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More Than Androgens: Hormonal and Paracrine Signaling in Prostate Development and Homeostasis

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Tissue-Specific Cell Signaling

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Abstract

The prostate is the major exocrine gland of the male reproductive system. The prostatic epithelium secretes an alkaline fluid, the prostatic fluid, that constitutes about 20–30% volume of the seminal fluid. It provides proteins and ions essential to control the ejaculation process and to regulate proteins involved in sperm maturation (e.g. human kallikrein-related peptidases, phosphatases, polyamines, pepsinogen II, citrate, glucose, and Zn2+, among others). The prostate exhibits some particularities when compared to other organs: it accumulates the highest levels of Zn2+ of any soft tissue; epithelial cells can produce energy by glycolysis (similarly to highly proliferative cells); and, it is the only gland that tends to grow with aging, being associated with disorders of elderly, such as benign prostatic hyperplasia and carcinoma. Prostate development starts early in embryogenesis, but prostate maturation is only concluded in puberty. Specification of the prostate during human embryogenesis occurs before clear morphological evidence of a developing structure and involves the expression of signaling molecules that drive cells from the urogenital sinus to a prostatic cell fate. Prostate development and homeostasis are regulated by several hormones and growth factors and are highly dependent on autocrine and paracrine signaling. Efforts have been made to identify the mediators of prostate signaling as revised in this chapter, however this has been compromised by experimental constrains. Furthermore, most of the studies has been performed in rodent models, which makes extrapolations to other species difficult, given the inter-species variability on prostate anatomy and morphology.

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Notes

  1. 1.

    AR-mutant mice, insensitive to androgens, that do not have prostate.

Abbreviations

ACPP:

Prostatic acid phosphatase

ADT:

Androgen deprivation therapy

AKT:

RAC-alpha serine/threonine-protein kinase

AR:

Androgen receptor

ARE:

Androgen response element

BAD:

Bcl2-associated agonist of cell death

BAG1:

BAG family molecular chaperone regulator 1

BAX:

Apoptosis regulator BAX

BCL2:

Apoptosis regulator Bcl-2

BMP:

Bone morphogenetic proteins

BPH:

Benign prostate hyperplasia

CASP1:

Activating caspase-1

CDKN1B:

Cyclin-dependent kinase inhibitor 1B

CGRP:

Calcitonin gene-related peptide

CRCP:

Castration-resistant prostate cancer

CTNNB:

Catenin beta-1

CYP17A1:

Steroid 17-alpha-hydroxylase/17, 20 lyase

DHT:

5α-dihydrotestosterone

DLL:

Delta-like protein

DNA:

Deoxyribonucleic acid

E:

Estrogens

E2:

17β-estradiol

ER:

Estrogen receptor

EGF:

Epidermal growth factor

EGFR:

EGF receptor

ERBB2:

Tyrosine-protein kinase erbB-2

FGF:

Fibroblast growth factor

FGFBP:

FGF-binding proteins

FGFR:

FGF receptor

FOS:

Proto-oncogene c-Fos

FOXO1:

Forkhead box protein O1

GPCR:

G protein-coupled receptor

GPER:

G protein-coupled estrogen receptor

GOT2:

Mitochondrial aspartate aminotransferase

HGF:

Hepatocyte growth factor

HIF1A:

Hypoxia-inducible factor 1-alpha

HSP:

Heat shock protein

IGF:

Insulin-like growth factor

IGFBP:

IGF-binding proteins

IL:

Interleukin

JAG:

Jagged protein

JAK:

Tyrosine-protein kinase JAK

JNK:

c-Jun NH2-terminal kinase

JUN:

Transcription factor AP-1

KGF:

Keratinocyte growth factor

KLK:

Kallikrein-related peptidase

KLK3:

Prostate-specific antigen (commonly known as PSA)

MAPK:

Mitogen-activated protein kinase

NKX3-1:

Homeobox protein Nkx-3.1

NOTCH:

Neurogenic locus notch homolog protein

OXT:

Oxytocin

OXTR:

OXT receptor

PCa:

Prostate cancer

PDGF:

Platelet-derived growth factor

PG:

Progesterone

PGR:

PG receptor

PI3K:

Phosphatidylinositol 3-kinase

PRKCA:

Protein kinase C alpha type

PRKCE:

Protein kinase C epsilon type

PRL:

Prolactin

PRLR:

PRL receptor

PTC:

Protein patched

PTK:

Focal adhesion kinase 1

RALA:

Ras-related protein Ral-A

ROS:

Reactive oxygen species

SFRP1:

Secreted frizzled-related protein 1

SHBG:

Sex hormone-binding globulin

SHH:

Sonic hedgehog protein

SMAD:

Mothers against decapentaplegic homolog

SOX9:

Transcription factor SOX-9

SRC:

Proto-oncogene tyrosine-protein kinase Src

SRD5A:

3-oxo-5-alpha-steroid 4-dehydrogenase 1

STAT:

Signal transducer and activator of transcription

T:

Testosterone

T3:

Triiodothyronine

T4:

Thyroxine

tfm:

Testicular feminization

TGF:

Transforming growth factor

TH:

Thyroid hormone

TRH:

Thyrotropin-releasing hormone

Tyr:

Tyrosine

UGE:

Urogenital sinus epithelium

UGM:

Urogenital sinus mesenchyme

UGS:

Urogenital sinus

VEGF:

Vascular endothelial growth factor

wt:

Wild-type

References

  1. Sharma M, Gupta S, Dhole B, Kumar A (2017) The prostate gland. In: Kumar A, Sharma M (eds) Basics of human andrology. Springer, Singapore, pp 17–35

    Chapter  Google Scholar 

  2. Francis JC, Swain A (2018) Prostate organogenesis. Cold Spring Harb Perspect Med 8:a030353. https://doi.org/10.1101/cshperspect.a030353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Toivanen R, Shen MM (2017) Prostate organogenesis: tissue induction, hormonal regulation and cell type specification. Development 144:1382–1398. https://doi.org/10.1242/dev.148270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Cunha GR (1985) Mesenchymal-epithelial interactions during androgen-induced development of the prostate. Prog Clin Biol Res 171:15–24

    CAS  PubMed  Google Scholar 

  5. Meeks JJ, Schaeffer EM (2008) Genetic regulation of prostate development. J Androl 32:210–217. https://doi.org/10.2164/jandrol.110.011577

    Article  CAS  Google Scholar 

  6. Prins GS, Putz O (2008) Molecular signaling pathways that regulate prostate gland development. Differentiation 76:641–659. https://doi.org/10.1111/j.1432-0436.2008.00277.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Verze P, Cai T, Lorenzetti S (2016) The role of the prostate in male fertility, health and disease. Nat Rev Urol 13:379–386. https://doi.org/10.1038/nrurol.2016.89

    Article  CAS  PubMed  Google Scholar 

  8. McNeal JE, Burroughs Wellcome Company (1983) The prostate gland, morphology and pathobiology. Published for Burroughs Wellcome Co., Princeton, NJ, by Custom Pub. Services, ©1983, Princeton, NJ

    Google Scholar 

  9. Montano M, Bushman W (2017) Morphoregulatory pathways in prostate ductal development. Dev Dyn 246:89–99. https://doi.org/10.1002/dvdy.24478

    Article  PubMed  Google Scholar 

  10. Timms BG (2008) Prostate development: a historical perspective. Differentiation 76:565–577. https://doi.org/10.1111/j.1432-0436.2008.00278.x

    Article  CAS  PubMed  Google Scholar 

  11. McNeal JE (1981) The zonal anatomy of the prostate. Prostate 2:35–49

    Article  CAS  PubMed  Google Scholar 

  12. Kurita T, Wang YZ, Donjacour AA et al (2001) Paracrine regulation of apoptosis by steroid hormones in the male and female reproductive system. Cell Death Differ 8:192–200. https://doi.org/10.1038/sj.cdd.4400797

    Article  CAS  PubMed  Google Scholar 

  13. Hägglöf C, Bergh A (2012) The stroma—a key regulator in prostate function and malignancy. Cancers (Basel) 4:531–548. https://doi.org/10.3390/cancers4020531

    Article  CAS  PubMed  Google Scholar 

  14. Thomson AA (2008) Mesenchymal mechanisms in prostate organogenesis. Differentiation 76:587–598. https://doi.org/10.1111/j.1432-0436.2008.00296.x

    Article  CAS  PubMed  Google Scholar 

  15. Bennett NC, Gardiner RA, Hooper JD et al (2010) Molecular cell biology of androgen receptor signalling. Int J Biochem Cell Biol 42:813–827. https://doi.org/10.1016/j.biocel.2009.11.013

    Article  CAS  PubMed  Google Scholar 

  16. Zhu Y-S (2005) Molecular basis of steroid action in the prostate. Cellscience 1:27–55. https://doi.org/10.1901/jaba.2005.1-27

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zhang B, Kwon O-J, Henry G et al (2016) Non-cell-autonomous regulation of prostate epithelial homeostasis by androgen receptor. Mol Cell 63:976–989. https://doi.org/10.1016/j.molcel.2016.07.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Xie Q, Liu Y, Cai T et al (2017) Dissecting cell-type-specific roles of androgen receptor in prostate homeostasis and regeneration through lineage tracing. Nat Commun 8:14284. https://doi.org/10.1038/ncomms14284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pihlajamaa P, Sahu B, Lyly L et al (2014) Tissue-specific pioneer factors associate with androgen receptor cistromes and transcription programs. EMBO J 33:312–326. https://doi.org/10.1002/embj.201385895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Pang S-T, Dillner K, Wu X et al (2002) Gene expression profiling of androgen deficiency predicts a pathway of prostate apoptosis that involves genes related to oxidative stress. Endocrinology 143:4897–4906. https://doi.org/10.1210/en.2002-220327

    Article  CAS  PubMed  Google Scholar 

  21. Vanpoucke G, Orr B, Grace OC et al (2007) Transcriptional profiling of inductive mesenchyme to identify molecules involved in prostate development and disease. Genome Biol 8:R213. https://doi.org/10.1186/gb-2007-8-10-r213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Nantermet PV, Xu J, Yu Y et al (2004) Identification of genetic pathways activated by the androgen receptor during the induction of proliferation in the ventral prostate gland. J Biol Chem 279:1310–1322. https://doi.org/10.1074/jbc.M310206200

    Article  CAS  PubMed  Google Scholar 

  23. Tanner MJ, Welliver RC, Chen M et al (2011) Effects of androgen receptor and androgen on gene expression in prostate stromal fibroblasts and paracrine signaling to prostate cancer cells. PLoS One 6:e16027. https://doi.org/10.1371/journal.pone.0016027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Risbridger GP, Ellem SJ, McPherson SJ (2007) Estrogen action on the prostate gland: a critical mix of endocrine and paracrine signaling. J Mol Endocrinol 39:183–188. https://doi.org/10.1677/JME-07-0053

    Article  CAS  PubMed  Google Scholar 

  25. Oettel M, Mukhopadhyay AK (2004) Progesterone: the forgotten hormone in men? Aging Male 7:236–257

    Google Scholar 

  26. Cooke PS, Nanjappa MK, Ko C et al (2017) Estrogens in male physiology. Physiol Rev 97:995–1043. https://doi.org/10.1152/physrev.00018.2016

    Article  PubMed  PubMed Central  Google Scholar 

  27. Vrtačnik P, Ostanek B, Mencej-Bedrač S, Marc J (2014) The many faces of estrogen signaling. Biochem Medica 24:329–342. https://doi.org/10.11613/BM.2014.035

  28. Hess RA, Cooke PS (2018) Estrogen in the male: a historical perspective. Biol Reprod 99:27–44. https://doi.org/10.1093/biolre/ioy043

    Article  PubMed  PubMed Central  Google Scholar 

  29. Grimm SL, Hartig SM, Edwards DP (2016) Progesterone receptor signaling mechanisms. J Mol Biol 428:3831–3849. https://doi.org/10.1016/j.jmb.2016.06.020

    Article  CAS  PubMed  Google Scholar 

  30. Wu W-F, Maneix L, Insunza J et al (2017) Estrogen receptor β, a regulator of androgen receptor signaling in the mouse ventral prostate. Proc Natl Acad Sci USA 114:E3816–E3822. https://doi.org/10.1073/pnas.1702211114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Grindstad T, Richardsen E, Andersen S et al (2018) Progesterone receptors in prostate cancer: progesterone receptor B is the isoform associated with disease progression. Sci Rep 8:11358. https://doi.org/10.1038/s41598-018-29520-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yu Y, Liu L, Xie N et al (2013) Expression and function of the progesterone receptor in human prostate stroma provide novel insights to cell proliferation control. J Clin Endocrinol Metab 98:2887–2896. https://doi.org/10.1210/jc.2012-4000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Goffin V, Hoang DT, Bogorad RL, Nevalainen MT (2011) Prolactin regulation of the prostate gland: a female player in a male game. Nat Rev Urol 8:597–607. https://doi.org/10.1038/nrurol.2011.143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Costello LC, Franklin RB (2002) Testosterone and prolactin regulation of metabolic genes and citrate metabolism of prostate epithelial cells. Horm Metab Res 34:417–424. https://doi.org/10.1055/s-2002-33598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nevalainen MT, Valve EM, Ingleton PM et al (1997) Prolactin and prolactin receptors are expressed and functioning in human prostate. J Clin Invest 99:618–627. https://doi.org/10.1172/JCI119204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Radhakrishnan A, Raju R, Tuladhar N et al (2012) A pathway map of prolactin signaling. J Cell Commun Signal 6:169–173. https://doi.org/10.1007/s12079-012-0168-0

    Article  PubMed  PubMed Central  Google Scholar 

  37. Farnsworth W, Slaunwhite WR, Sharma M et al (1981) Interaction of prolactin and testosterone in the human prostate. Urol Res 9:79–88. https://doi.org/10.1007/BF00256681

    Article  CAS  PubMed  Google Scholar 

  38. Vekemans M, Robyn C (1975) Influence of age on serum prolactin levels in women and men. Br Med J 4:738–739. https://doi.org/10.1136/bmj.4.5999.738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hernandez ME, Soto-Cid A, Rojas F et al (2006) Prostate response to prolactin in sexually active male rats. Reprod Biol Endocrinol 4:28. https://doi.org/10.1186/1477-7827-4-28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Rouet V, Bogorad RL, Kayser C et al (2010) Local prolactin is a target to prevent expansion of basal/stem cells in prostate tumors. Proc Natl Acad Sci USA 107:15199–15204. https://doi.org/10.1073/pnas.0911651107

    Article  PubMed  PubMed Central  Google Scholar 

  41. Whittington K, Assinder S, Gould M, Nicholson H (2004) Oxytocin, oxytocin-associated neurophysin and the oxytocin receptor in the human prostate. Cell Tissue Res 318:375–382. https://doi.org/10.1007/s00441-004-0968-5

    Article  CAS  PubMed  Google Scholar 

  42. Chatterjee O, Patil K, Sahu A et al (2016) An overview of the oxytocin-oxytocin receptor signaling network. J Cell Commun Signal 10:355–360. https://doi.org/10.1007/s12079-016-0353-7

    Article  PubMed  PubMed Central  Google Scholar 

  43. Nicholson HD, Whittington K (2007) Oxytocin and the human prostate in health and disease. In: International review of cytology, pp 253–286

    Google Scholar 

  44. Thackare H, Nicholson HD, Whittington K (2006) Oxytocin—its role in male reproduction and new potential therapeutic uses. Hum Reprod Update 12:437–448. https://doi.org/10.1093/humupd/dmk002

    Article  CAS  PubMed  Google Scholar 

  45. Assinder SJ, Nicholson HD (2004) Effects of steroids on oxytocin secretion by the human prostate in vitro. Int J Androl 27:12–18. https://doi.org/10.1111/j.1365-2605.2004.00439.x

    Article  CAS  PubMed  Google Scholar 

  46. Whittington K, Connors B, King K et al (2007) The effect of oxytocin on cell proliferation in the human prostate is modulated by gonadal steroids: implications for benign prostatic hyperplasia and carcinoma of the prostate. Prostate 67:1132–1142. https://doi.org/10.1002/pros.20612

    Article  CAS  PubMed  Google Scholar 

  47. Xu H, Fu S, Chen Y et al (2017) Oxytocin: its role in benign prostatic hyperplasia via the ERK pathway. Clin Sci (Lond) 131:595–607. https://doi.org/10.1042/CS20170030

    Article  CAS  PubMed  Google Scholar 

  48. Xu H, Fu S, Chen Q et al (2017) The function of oxytocin: a potential biomarker for prostate cancer diagnosis and promoter of prostate cancer. Oncotarget 8:31215–31226. https://doi.org/10.18632/oncotarget.16107

  49. Bhasin S, Pekary AE, Brunskill B et al (1984) Hormonal control of prostatic thyrotropin-releasing hormone (TRH) testosterone modulates prostatic TRH concentrations. Endocrinology 114:946–950. https://doi.org/10.1210/endo-114-3-946

    Article  CAS  PubMed  Google Scholar 

  50. Pekary AE, Bhasin S, Smith V et al (1987) Thyroid hormone modulation of thyrotrophin-releasing hormone (TRH) and TRH-Gly levels in the male rat reproductive system. J Endocrinol 114:271–277

    Article  CAS  PubMed  Google Scholar 

  51. Pekary AE, Knoble M, Garcia N (1989) Thyrotropin-releasing hormone (TRH)-Gly conversion to TRH in rat ventral prostate is inhibited by castration and aging. Endocrinology 125:679–685. https://doi.org/10.1210/endo-125-2-679

    Article  CAS  PubMed  Google Scholar 

  52. Mani Maran RR, Subramanian S, Rajendiran G et al (1998) Prostate-thyroid axis: stimulatory effects of ventral prostate secretions on thyroid function. Prostate 36:8–13. https://doi.org/10.1002/(SICI)1097-0045(19980615)36:1%3c8:AID-PROS2%3e3.0.CO;2-F

    Article  CAS  PubMed  Google Scholar 

  53. Sakurai A, Nakai A, DeGroot LJ (1989) Expression of three forms of thyroid hormone receptor in human tissues. Mol Endocrinol 3:392–399. https://doi.org/10.1210/mend-3-2-392

    Article  CAS  PubMed  Google Scholar 

  54. Aruldhas MM, Ramalingam N, Jaganathan A et al (2010) Gestational and neonatal-onset hypothyroidism alters androgen receptor status in rat prostate glands at adulthood. Prostate 70:689–700. https://doi.org/10.1002/pros.21101

    Article  CAS  PubMed  Google Scholar 

  55. Yeh JY, Tsai SC, Kau MM et al (1999) Effects of thyroid hormones on the release of calcitonin gene-related peptide (CGRP) by rat prostate glands in vitro. Chin J Physiol 42:89–94

    CAS  PubMed  Google Scholar 

  56. Abrahamsson P-A, Dizeyi N, Alm P et al (2000) Calcitonin and calcitonin gene-related peptide in the human prostate gland. Prostate 44:181–186. https://doi.org/10.1002/1097-0045(20000801)44:3%3c181:AID-PROS1%3e3.0.CO;2-L

    Article  CAS  PubMed  Google Scholar 

  57. Latif A, Nakhla AM (1994) Calcitonin releases acid phosphatase from rat ventral prostate explants. Life Sci 54:561–565. https://doi.org/10.1016/0024-3205(94)90007-8

    Article  CAS  PubMed  Google Scholar 

  58. Warrington JI, Richards GO, Wang N (2017) The role of the calcitonin peptide family in prostate cancer and bone metastasis. Curr Mol Biol Reports 3:197–203. https://doi.org/10.1007/s40610-017-0071-9

    Article  Google Scholar 

  59. Maran RR, Aruldhas MM, Udhayakumar RC et al (1998) Impact of altered thyroid hormone status on prostatic glycosidases. Int J Androl 21:121–128. https://doi.org/10.1111/j.1365-2605.1998.00094.x

    Article  CAS  PubMed  Google Scholar 

  60. Hsieh M-L, Juang H-H (2005) Cell growth effects of triiodothyronine and expression of thyroid hormone receptor in prostate carcinoma cells. J Androl 26:422–428. https://doi.org/10.2164/jandrol.04162

    Article  CAS  PubMed  Google Scholar 

  61. Zhang S, Hsieh ML, Zhu W et al (1999) Interactive effects of triiodothyronine and androgens on prostate cell growth and gene expression. Endocrinology 140:1665–1671. https://doi.org/10.1210/endo.140.4.6666

    Article  CAS  PubMed  Google Scholar 

  62. Cotton LM, O’Bryan MK, Hinton BT (2008) Cellular signaling by fibroblast growth factors (FGFs) and their receptors (FGFRs) in male reproduction. Endocr Rev 29:193–216. https://doi.org/10.1210/er.2007-0028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Culig Z, Hobisch A, Cronauer MV et al (1996) Regulation of prostatic growth and function by peptide growth factors. Prostate 28:392–405. https://doi.org/10.1002/(SICI)1097-0045(199606)28:6%3c392:AID-PROS9%3e3.0.CO;2-C

    Article  CAS  PubMed  Google Scholar 

  64. Dahiya R, Lee C, Haughney PC et al (1996) Differential gene expression of transforming growth factors alpha and beta, epidermal growth factor, keratinocyte growth factor, and their receptors in fetal and adult human prostatic tissues and cancer cell lines. Urology 48:963–970

    Article  CAS  PubMed  Google Scholar 

  65. Ittmann M (2018) Anatomy and histology of the human and murine prostate. Cold Spring Harb Perspect Med 8:a030346. https://doi.org/10.1101/cshperspect.a030346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Lin Y, Wang F (2010) FGF signalling in prostate development, tissue homoeostasis and tumorigenesis. Biosci Rep 30:285–291. https://doi.org/10.1042/BSR20100020

    Article  CAS  PubMed  Google Scholar 

  67. Story MT (1995) Regulation of prostate growth by fibroblast growth factors. World J Urol 13:297–305

    Article  CAS  PubMed  Google Scholar 

  68. Kuslak SL, Marker PC (2007) Fibroblast growth factor receptor signaling through MEK–ERK is required for prostate bud induction. Differentiation 75:638–651. https://doi.org/10.1111/j.1432-0436.2006.00161.x

    Article  CAS  PubMed  Google Scholar 

  69. Huang Y, Hamana T, Liu J et al (2015) Type 2 fibroblast growth factor receptor signaling preserves stemness and prevents differentiation of prostate stem cells from the basal compartment. J Biol Chem 290:17753–17761. https://doi.org/10.1074/jbc.M115.661066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Roghani M, Moscatelli D (2007) Prostate cells express two isoforms of fibroblast growth factor receptor 1 with different affinities for fibroblast growth factor-2. Prostate 67:115–124. https://doi.org/10.1002/pros.20448

    Article  CAS  PubMed  Google Scholar 

  71. Peehl DM, Rubin JS (1995) Keratinocyte growth factor: an androgen-regulated mediator of stromal-epithelial interactions in the prostate. World J Urol 13:312–317

    Article  CAS  PubMed  Google Scholar 

  72. Planz B, Wang Q, Kirley SD et al (2001) Regulation of keratinocyte growth factor receptor and androgen receptor in epithelial cells of the human prostate. J Urol 166:678–683

    Article  CAS  PubMed  Google Scholar 

  73. Kim HG, Kassis J, Souto JC et al (1999) EGF receptor signaling in prostate morphogenesis and tumorigenesis. Histol Histopathol 14:1175–1182. https://doi.org/10.14670/HH-14.1175

  74. Sherwood ER, Lee C (1995) Epidermal growth factor-related peptides and the epidermal growth factor receptor in normal and malignant prostate. World J Urol 13:290–296

    Article  CAS  PubMed  Google Scholar 

  75. Poncet N, Guillaume J, Mouchiroud G (2011) Epidermal growth factor receptor transactivation is implicated in IL-6-induced proliferation and ERK1/2 activation in non-transformed prostate epithelial cells. Cell Signal 23:572–578. https://doi.org/10.1016/j.cellsig.2010.11.009

    Article  CAS  PubMed  Google Scholar 

  76. Yu S, Zhang C, Lin C-C et al (2011) Altered prostate epithelial development and IGF-1 signal in mice lacking the androgen receptor in stromal smooth muscle cells. Prostate 71:517–524. https://doi.org/10.1002/pros.21264

    Article  CAS  PubMed  Google Scholar 

  77. Heidegger I, Ofer P, Doppler W et al (2012) Diverse functions of IGF/Insulin signaling in malignant and noncancerous prostate cells: proliferation in cancer cells and differentiation in noncancerous cells. Endocrinology 153:4633–4643. https://doi.org/10.1210/en.2012-1348

    Article  CAS  PubMed  Google Scholar 

  78. Reynolds AR, Kyprianou N (2006) Growth factor signalling in prostatic growth: significance in tumour development and therapeutic targeting. Br J Pharmacol 147(Suppl):S144–S152. https://doi.org/10.1038/sj.bjp.0706635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Song K, Shankar E, Yang J et al (2013) Critical role of a survivin/TGF-β/mTORC1 axis in IGF-I-mediated growth of prostate epithelial cells. PLoS One 8:e61896. https://doi.org/10.1371/journal.pone.0061896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Tomlinson DC, Freestone SH, Grace OC, Thomson AA (2004) Differential effects of transforming growth factor-beta1 on cellular proliferation in the developing prostate. Endocrinology 145:4292–4300. https://doi.org/10.1210/en.2004-0526

    Article  CAS  PubMed  Google Scholar 

  81. Danielpour D (2005) Functions and regulation of transforming growth factor-beta (TGF-β) in the prostate. Eur J Cancer 41:846–857. https://doi.org/10.1016/j.ejca.2004.12.027

    Article  CAS  PubMed  Google Scholar 

  82. Ball EM, Risbridger GP (2001) Activins as regulators of branching morphogenesis. Dev Biol 238:1–12. https://doi.org/10.1006/dbio.2001.0399

    Article  CAS  PubMed  Google Scholar 

  83. Shimasaki S, Moore RK, Otsuka F, Erickson GF (2004) The bone morphogenetic protein system in mammalian reproduction. Endocr Rev 25:72–101. https://doi.org/10.1210/er.2003-0007

    Article  CAS  PubMed  Google Scholar 

  84. Omori A, Miyagawa S, Ogino Y et al (2014) Essential roles of epithelial bone morphogenetic protein signaling during prostatic development. Endocrinology 155:2534–2544. https://doi.org/10.1210/en.2013-2054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Valdez JM, Zhang L, Su Q et al (2012) Notch and TGFβ form a reciprocal positive regulatory loop that suppresses murine prostate basal stem/progenitor cell activity. Cell Stem Cell 11:676–688. https://doi.org/10.1016/j.stem.2012.07.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. McMahon AP, Ingham PW, Tabin CJ (2003) Developmental roles and clinical significance of Hedgehog signaling. In: Current topics in developmental biology. Academic Press, pp 1–114

    Google Scholar 

  87. Petrova R, Joyner AL (2014) Roles for Hedgehog signaling in adult organ homeostasis and repair. Development 141:3445–3457. https://doi.org/10.1242/dev.083691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Yu M, Bushman W (2013) Differential stage-dependent regulation of prostatic epithelial morphogenesis by Hedgehog signaling. Dev Biol 380:87–98. https://doi.org/10.1016/j.ydbio.2013.04.032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Doles J, Cook C, Shi X et al (2006) Functional compensation in Hedgehog signaling during mouse prostate development. Dev Biol 295:13–25. https://doi.org/10.1016/j.ydbio.2005.12.002

    Article  CAS  PubMed  Google Scholar 

  90. Lamm MLG, Catbagan WS, Laciak RJ et al (2002) Sonic hedgehog activates mesenchymal Gli1 expression during prostate ductal bud formation. Dev Biol 249:349–366. https://doi.org/10.1006/dbio.2002.0774

    Article  CAS  PubMed  Google Scholar 

  91. Yu M, Gipp J, Yoon JW et al (2009) Sonic hedgehog-responsive genes in the fetal prostate. J Biol Chem 284:5620–5629. https://doi.org/10.1074/jbc.M809172200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Wang B-E, Shou J, Ross S et al (2003) Inhibition of epithelial ductal branching in the prostate by sonic hedgehog is indirectly mediated by stromal cells. J Biol Chem 278:18506–18513. https://doi.org/10.1074/jbc.M300968200

    Article  CAS  PubMed  Google Scholar 

  93. Pu Y, Huang L, Prins GS (2004) Sonic hedgehog-patched Gli signaling in the developing rat prostate gland: lobe-specific suppression by neonatal estrogens reduces ductal growth and branching. Dev Biol 273:257–275. https://doi.org/10.1016/j.ydbio.2004.06.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Bushman W (2016) Hedgehog signaling in prostate development, regeneration and cancer. J Dev Biol 4:30. https://doi.org/10.3390/jdb4040030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Peng Y-C, Levine CM, Zahid S et al (2013) Sonic hedgehog signals to multiple prostate stromal stem cells that replenish distinct stromal subtypes during regeneration. Proc Natl Acad Sci USA 110:20611–20616. https://doi.org/10.1073/pnas.1315729110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Peng Y-C, Joyner AL (2015) Hedgehog signaling in prostate epithelial–mesenchymal growth regulation. Dev Biol 400:94–104. https://doi.org/10.1016/j.ydbio.2015.01.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Hori K, Sen A, Artavanis-Tsakonas S (2013) Notch signaling at a glance. J Cell Sci 126:2135–2140. https://doi.org/10.1242/jcs.127308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Leong KG, Gao W-Q (2008) The Notch pathway in prostate development and cancer. Differentiation 76:699–716. https://doi.org/10.1111/j.1432-0436.2008.00288.x

    Article  CAS  PubMed  Google Scholar 

  99. Deng G, Ma L, Meng Q et al (2016) Notch signaling in the prostate: critical roles during development and in the hallmarks of prostate cancer biology. J Cancer Res Clin Oncol 142:531–547. https://doi.org/10.1007/s00432-015-1946-x

    Article  CAS  PubMed  Google Scholar 

  100. Wang X-D, Leow CC, Zha J et al (2006) Notch signaling is required for normal prostatic epithelial cell proliferation and differentiation. Dev Biol 290:66–80. https://doi.org/10.1016/j.ydbio.2005.11.009

    Article  CAS  PubMed  Google Scholar 

  101. Belandia B, Powell SM, García-Pedrero JM et al (2005) Hey1, a mediator of notch signaling, is an androgen receptor corepressor. Mol Cell Biol 25:1425–1436. https://doi.org/10.1128/MCB.25.4.1425-1436.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Wang X-D, Shou J, Wong P et al (2004) Notch1-expressing cells are indispensable for prostatic branching morphogenesis during development and re-growth following castration and androgen replacement. J Biol Chem 279:24733–24744. https://doi.org/10.1074/jbc.M401602200

    Article  CAS  PubMed  Google Scholar 

  103. Komiya Y, Habas R (2008) Wnt signal transduction pathways. Organogenesis 4:68–75. https://doi.org/10.4161/org.4.2.5851

    Article  PubMed  PubMed Central  Google Scholar 

  104. Zhang T-J, Hoffman BG, Ruiz de Algara T, Helgason CD (2006) SAGE reveals expression of Wnt signalling pathway members during mouse prostate development. Gene Expr Patterns 6:310–324. https://doi.org/10.1016/j.modgep.2005.07.005

    Article  CAS  PubMed  Google Scholar 

  105. Simons BW, Hurley PJ, Huang Z et al (2012) Wnt signaling though beta-catenin is required for prostate lineage specification. Dev Biol 371:246–255. https://doi.org/10.1016/j.ydbio.2012.08.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Mehta V, Abler LL, Keil KP et al (2011) Atlas of Wnt and R-spondin gene expression in the developing male mouse lower urogenital tract. Dev Dyn 240:2548–2560. https://doi.org/10.1002/dvdy.22741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Mehta V, Schmitz CT, Keil KP et al (2013) Beta-catenin (CTNNB1) induces Bmp expression in urogenital sinus epithelium and participates in prostatic bud initiation and patterning. Dev Biol 376:125–135. https://doi.org/10.1016/j.ydbio.2013.01.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Kruithof-de Julio M, Shibata M, Desai N et al (2013) Canonical Wnt signaling regulates Nkx3.1 expression and luminal epithelial differentiation during prostate organogenesis. Dev Dyn 242:1160–1171. https://doi.org/10.1002/dvdy.24008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Wang B-E, Wang X-D, Ernst JA et al (2008) Regulation of epithelial branching morphogenesis and cancer cell growth of the prostate by Wnt signaling. PLoS One 3:e2186. https://doi.org/10.1371/journal.pone.0002186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Gómez-Orte E, Sáenz-Narciso B, Moreno S, Cabello J (2013) Multiple functions of the noncanonical Wnt pathway. Trends Genet 29:545–553. https://doi.org/10.1016/j.tig.2013.06.003

    Article  CAS  PubMed  Google Scholar 

  111. Huang L, Pu Y, Hu WY et al (2009) The role of Wnt5a in prostate gland development. Dev Biol 328:188–199. https://doi.org/10.1016/j.ydbio.2009.01.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Joesting MS, Perrin S, Elenbaas B et al (2005) Identification of SFRP1 as a candidate mediator of stromal-to-epithelial signaling in prostate cancer. Cancer Res 65:10423–10430. https://doi.org/10.1158/0008-5472.CAN-05-0824

    Article  CAS  PubMed  Google Scholar 

  113. Joesting MS, Cheever TR, Volzing KG et al (2008) Secreted frizzled related protein 1 is a paracrine modulator of epithelial branching morphogenesis, proliferation, and secretory gene expression in the prostate. Dev Biol 317:161–173. https://doi.org/10.1016/j.ydbio.2008.02.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Uhlén M, Fagerberg L, Hallström BM et al (2015) Proteomics. Tissue-based map of the human proteome. Science 347:1260419. https://doi.org/10.1126/science.1260419

  115. Borchert A, Leavitt DA (2018) A review of male sexual health and dysfunction following surgical treatment for benign prostatic hyperplasia and lower urinary tract symptoms. Curr Urol Rep 19:66. https://doi.org/10.1007/s11934-018-0813-0

    Article  PubMed  Google Scholar 

  116. International Agency for Research on Cancer (2018) GLOBOCAN 2018—estimated number of cases worldwide, males, all ages. In: Global cancer observatory. http://gco.iarc.fr/

  117. Huggins C, Stevens R, Hodges CV (1941) Studies on prostatic cancer II. The effects of castration on advanced carcinoma of the prostate gland. Arch Surg 43:209. https://doi.org/10.1001/archsurg.1941.01210140043004

  118. Basu S, Tindall DJ (2010) Androgen action in prostate cancer. Horm Cancer 1:223–228. https://doi.org/10.1007/s12672-010-0044-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Chen Y, Sawyers CL, Scher HI (2008) Targeting the androgen receptor pathway in prostate cancer. Curr Opin Pharmacol 8:440–448. https://doi.org/10.1016/j.coph.2008.07.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Knudsen KE, Penning TM (2010) Partners in crime: deregulation of AR activity and androgen synthesis in prostate cancer. Trends Endocrinol Metab 21:315–324. https://doi.org/10.1016/j.tem.2010.01.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Knudsen KE, Scher HI (2009) Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clin Cancer Res 15:4792–4798. https://doi.org/10.1158/1078-0432.CCR-08-2660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. de Bono JS, Logothetis CJ, Molina A et al (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364:1995–2005. https://doi.org/10.1056/NEJMoa1014618

    Article  PubMed  PubMed Central  Google Scholar 

  123. Ryan CJ, Smith MR, Fizazi K et al (2015) Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 16:152–160. https://doi.org/10.1016/S1470-2045(14)71205-7

    Article  CAS  PubMed  Google Scholar 

  124. Scher HI, Fizazi K, Saad F et al (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367:1187–1197. https://doi.org/10.1056/NEJMoa1207506

    Article  CAS  PubMed  Google Scholar 

  125. Beer TM, Armstrong AJ, Rathkopf DE et al (2014) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371:424–433. https://doi.org/10.1056/NEJMoa1405095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Arora VK, Schenkein E, Murali R et al (2013) Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell 155:1309–1322. https://doi.org/10.1016/j.cell.2013.11.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Watson PA, Arora VK, Sawyers CL (2015) Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat Rev Cancer 15:701–711. https://doi.org/10.1038/nrc4016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Li Q, Deng Q, Chao H-P et al (2018) Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses. Nat Commun 9:3600. https://doi.org/10.1038/s41467-018-06067-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Culig Z, Hobisch A, Cronauer MV et al (1994) Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res 54:5474–5478

    CAS  PubMed  Google Scholar 

  130. Liu Y, Karaca M, Zhang Z et al (2010) Dasatinib inhibits site-specific tyrosine phosphorylation of androgen receptor by Ack1 and Src kinases. Oncogene 29:3208–3216. https://doi.org/10.1038/onc.2010.103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Brass AL, Barnard J, Patai BL et al (1995) Androgen up-regulates epidermal growth factor receptor expression and binding affinity in PC3 cell lines expressing the human androgen receptor. Cancer Res 55:3197–3203

    CAS  PubMed  Google Scholar 

  132. Ye D, Mendelsohn J, Fan Z (1999) Androgen and epidermal growth factor down-regulate cyclin-dependent kinase inhibitor p27Kip1 and costimulate proliferation of MDA PCa 2a and MDA PCa 2b prostate cancer cells. Clin Cancer Res 5:2171–2177

    CAS  PubMed  Google Scholar 

  133. Ueda T, Bruchovsky N, Sadar MD (2002) Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways. J Biol Chem 277:7076–7085. https://doi.org/10.1074/jbc.M108255200

    Article  CAS  PubMed  Google Scholar 

  134. Liu Y, Majumder S, McCall W et al (2005) Inhibition of HER-2/neu kinase impairs androgen receptor recruitment to the androgen responsive enhancer. Cancer Res 65:3404–3409. https://doi.org/10.1158/0008-5472.CAN-04-4292

    Article  CAS  PubMed  Google Scholar 

  135. Mahajan NP, Liu Y, Majumder S et al (2007) Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation. Proc Natl Acad Sci 104:8438–8443. https://doi.org/10.1073/pnas.0700420104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Moschos SJ, Mantzoros CS (2002) The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncology 63:317–332. https://doi.org/10.1159/000066230

    Article  CAS  PubMed  Google Scholar 

  137. Wu Y, Zhao W, Zhao J et al (2007) Identification of androgen response elements in the insulin-like growth factor I upstream promoter. Endocrinology 148:2984–2993. https://doi.org/10.1210/en.2006-1653

    Article  CAS  PubMed  Google Scholar 

  138. Ragel BT, Couldwell WT, Gillespie DL, Jensen RL (2007) Identification of hypoxia-induced genes in a malignant glioma cell line (U-251) by cDNA microarray analysis. Neurosurg Rev 30:181–187. https://doi.org/10.1007/s10143-007-0070-z

    Article  PubMed  Google Scholar 

  139. Yoshizawa A, Ogikubo S (2006) IGF binding protein-5 synthesis is regulated by testosterone through transcriptional mechanisms in androgen responsive cells. Endocr J 53:811–818

    Article  CAS  PubMed  Google Scholar 

  140. Hayes SA, Zarnegar M, Sharma M et al (2001) SMAD3 represses androgen receptor-mediated transcription. Cancer Res 61:2112–2118

    CAS  PubMed  Google Scholar 

  141. Kang H-Y, Huang K-E, Chang SY et al (2002) Differential Modulation of androgen receptor-mediated transactivation by Smad3 and tumor suppressor Smad4. J Biol Chem 277:43749–43756. https://doi.org/10.1074/jbc.M205603200

    Article  CAS  PubMed  Google Scholar 

  142. Bruckheimer EM, Kyprianou N (2001) Dihydrotestosterone enhances transforming growth factor-beta-induced apoptosis in hormone-sensitive prostate cancer cells. Endocrinology 142:2419–2426. https://doi.org/10.1210/endo.142.6.8218

    Article  CAS  PubMed  Google Scholar 

  143. Chipuk JE, Cornelius SC, Pultz NJ et al (2002) The androgen receptor represses transforming growth factor-beta signaling through interaction with Smad3. J Biol Chem 277:1240–1248. https://doi.org/10.1074/jbc.M108855200

    Article  CAS  PubMed  Google Scholar 

  144. Memarzadeh S, Xin L, Mulholland DJ et al (2007) Enhanced paracrine FGF10 expression promotes formation of multifocal prostate adenocarcinoma and an increase in epithelial androgen receptor. Cancer Cell 12:572–585. https://doi.org/10.1016/j.ccr.2007.11.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Rosini P, Bonaccorsi L, Baldi E et al (2002) Androgen receptor expression induces FGF2, FGF-binding protein production, and FGF2 release in prostate carcinoma cells: role of FGF2 in growth, survival, and androgen receptor down-modulation. Prostate 53:310–321. https://doi.org/10.1002/pros.10164

    Article  CAS  PubMed  Google Scholar 

  146. Mabjeesh NJ, Escuin D, LaVallee TM et al (2003) 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell 3:363–375

    Article  CAS  PubMed  Google Scholar 

  147. Rinaldo F, Li J, Wang E et al (2007) RalA regulates vascular endothelial growth factor-C (VEGF-C) synthesis in prostate cancer cells during androgen ablation. Oncogene 26:1731–1738. https://doi.org/10.1038/sj.onc.1209971

    Article  CAS  PubMed  Google Scholar 

  148. Culig Z, Santer FR (2014) Androgen receptor signaling in prostate cancer. Cancer Metastasis Rev 33:413–427. https://doi.org/10.1007/s10555-013-9474-0

    Article  CAS  PubMed  Google Scholar 

  149. Guo Z, Dai B, Jiang T et al (2006) Regulation of androgen receptor activity by tyrosine phosphorylation. Cancer Cell 10:309–319. https://doi.org/10.1016/j.ccr.2006.08.021

    Article  CAS  PubMed  Google Scholar 

  150. Lee L-F, Louie MC, Desai SJ et al (2004) Interleukin-8 confers androgen-independent growth and migration of LNCaP: differential effects of tyrosine kinases Src and FAK. Oncogene 23:2197–2205. https://doi.org/10.1038/sj.onc.1207344

    Article  CAS  PubMed  Google Scholar 

  151. Lager DJ, Goeken JA, Kemp JD, Robinson RA (1988) Squamous metaplasia of the prostate: an immunohistochemical study. Am J Clin Pathol 90:597–601. https://doi.org/10.1093/ajcp/90.5.597

    Article  CAS  PubMed  Google Scholar 

  152. Risbridger GP, Wang H, Frydenberg M, Cunha G (2001) The metaplastic effects of estrogen on mouse prostate epithelium: proliferation of cells with basal cell phenotype. Endocrinology 142:2443–2450. https://doi.org/10.1210/endo.142.6.8171

    Article  CAS  PubMed  Google Scholar 

  153. Risbridger G, Wang H, Young P et al (2001) Evidence that epithelial and mesenchymal estrogen receptor-alpha mediates effects of estrogen on prostatic epithelium. Dev Biol 229:432–442. https://doi.org/10.1006/dbio.2000.9994

    Article  CAS  PubMed  Google Scholar 

  154. Morais-Santos M, Nunes AEB, Oliveira AG et al (2015) Changes in estrogen receptor ERβ (ESR2) expression without changes in the estradiol levels in the prostate of aging rats. PLoS One 10:e0131901. https://doi.org/10.1371/journal.pone.0131901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Zhao Z, Yu H, Kong Q et al (2017) Effect of ERβ-regulated ERK1/2 signaling on biological behaviors of prostate cancer cells. Am J Transl Res 9:2775–2787

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors would like to acknowledge the support of the Institute for Biomedicine—iBiMED (UID/BIM/04501/2013 and UID/BIM/04501/2019) and POCI-01-0145-FEDER-007628), supported by the Portuguese Foundation for Science and Technology (FCT), Compete2020 and FEDER fund, and of the Programa Operacional Competitividade e Internacionalização (POCI), in the component FEDER, and by national funds (OE) through FCT/MCTES, in the scope of the project HyTherCaP (PTDC/MECONC/29030/2017). This work was also financed by FEDER funds through the “Programa Operacional Competitividade e Internacionalização—COMPETE 2020” and by National Funds through the FCT—Fundação para a Ciência e Tecnologia (PTDC/DTPDES/6077/2014). Juliana Felgueiras was supported by an individual grant from FCT of the Portuguese Ministry of Science and Higher Education (SFRH/BD/102981/2014). The HyTherCaP project is also acknowledged for the junior researcher contract of Vânia Camilo.

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Authors and Affiliations

  1. Laboratory of Signal Transduction, Department of Medical Sciences, iBiMED—Institute of Biomedicine, University of Aveiro, Aveiro, Portugal

    Juliana Felgueiras & Margarida Fardilha

  2. Cancer Biology and Epigenetics Group—Research Center, Portuguese Oncology Institute of Porto, Porto, Portugal

    Juliana Felgueiras, Vânia Camilo & Carmen Jerónimo

  3. Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal

    Carmen Jerónimo

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  1. Juliana Felgueiras
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  2. Vânia Camilo
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Correspondence to Carmen Jerónimo .

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  1. Laboratory of Signal Transduction, Department of Medical Sciences, Institute of Biomedicine—iBiMED, University of Aveiro, Aveiro, Portugal

    Joana Vieira Silva

  2. Laboratory of Protein Phosphorylation and Proteomics, Department of Cellular and Molecular Medicine, Faculty of Medicine, KU Leuven, Leuven, Belgium

    Maria João Freitas

  3. Laboratory of Signal Transduction, Department of Medical Sciences, Institute of Biomedicine—iBiMED, University of Aveiro, Aveiro, Portugal

    Margarida Fardilha

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Felgueiras, J., Camilo, V., Fardilha, M., Jerónimo, C. (2020). More Than Androgens: Hormonal and Paracrine Signaling in Prostate Development and Homeostasis. In: Silva, J.V., Freitas, M.J., Fardilha, M. (eds) Tissue-Specific Cell Signaling. Springer, Cham. https://doi.org/10.1007/978-3-030-44436-5_7

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