Skip to main content

Advertisement

SpringerLink
Log in

Regulation of Prolactin Receptor Levels and Activity in Breast Cancer

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

From its traditional identity as a hormone involved in growth and differentiation of mammary epithelium and in lactation, to having a pertinent role in the development of mammary carcinoma, the peptide hormone/cytokine prolactin (PRL) has emerged as a versatile signaling molecule. There has been significant progress in our understanding of the fine working of PRL in the past several years. Notably, much effort has been concentrated on the mediator of PRL action, namely, the prolactin receptor (PRLr). The causal link between increased PRLr expression and breast cancer is being increasingly appreciated. Considering that the level of the receptor on the surface is a critical determinant of signaling output in response to PRL, the uncovering of regulatory elements that control receptor expression becomes important. The principle focus of this review is on the regulation of PRLr expression and activity in breast cancer with a brief overview of different isoforms of PRLr, their expression, signaling capabilities and the biological outcomes of PRL/PRLr signaling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1

Similar content being viewed by others

Abbreviations

PRLr:

prolactin receptor

PRL:

prolactin

Jak:

Janus kinase

GEF:

guanine nucleotide exchange factor

ECD:

extracellular domain

ICD:

intracellular domain

TM:

transmembrane domain

FAK:

focal adhesion kinase

EGFR:

epidermal growth factor receptor

PRLBP:

Prolactin binding protein

E2:

estradiol

ER:

estrogen receptor

ANA:

anandamide

TCDD:

2,3,7,8-tetrachlorodibenzo-p-dioxin

Ah:

aryl hydrocarbon

GHR:

growth hormone receptor

EpoR:

erythropoietin receptor

IFNAR1:

type I interferon receptor

TpoR:

thrombopoietin receptor

RTK:

receptor tyrosine kinase

References

  1. Rui H, Lebrun JJ, Kirken RA, Kelly PA, Farrar WL. JAK2 activation and cell proliferation induced by antibody-mediated prolactin receptor dimerization. Endocrinology 1994;135(4):1299–306.

    Article  PubMed  CAS  Google Scholar 

  2. Rui H, Kirken RA, Farrar WL. Activation of receptor-associated tyrosine kinase JAK2 by prolactin. J Biol Chem 1994;269(7):5364–8.

    PubMed  CAS  Google Scholar 

  3. Clevenger CV, Furth PA, Hankinson SE, Schuler LA. The role of prolactin in mammary carcinoma. Endocr Rev 2003;24(1):1–27.

    Article  PubMed  CAS  Google Scholar 

  4. Clevenger CV, Kline JB. Prolactin receptor signal transduction. Lupus 2001;10(10):706–18.

    Article  PubMed  CAS  Google Scholar 

  5. Chilton BS, Hewetson A. Prolactin and growth hormone signaling. Curr Top Dev Biol 2005;68:1–23.

    Article  PubMed  CAS  Google Scholar 

  6. Das R, Vonderhaar BK. Activation of raf-1, MEK, and MAP kinase in prolactin responsive mammary cells. Breast Cancer Res Treat 1996;40(2):141–9.

    Article  PubMed  CAS  Google Scholar 

  7. Olazabal I, Munoz J, Ogueta S, Obregon E, Garcia-Ruiz JP. Prolactin (PRL)-PRL receptor system increases cell proliferation involving JNK (c-Jun amino terminal kinase) and AP-1 activation: inhibition by glucocorticoids. Mol Endocrinol 2000;14(4):564–75.

    Article  PubMed  CAS  Google Scholar 

  8. Cheng Y, Zhizhin I, Perlman RL, Mangoura D. Prolactin-induced cell proliferation in PC12 cells depends on JNK but not ERK activation. J Biol Chem 2000;275(30):23326–32.

    Article  PubMed  CAS  Google Scholar 

  9. Schwertfeger KL, Hunter S, Heasley LE, Levresse V, Leon RP, DeGregori J, et al. Prolactin stimulates activation of c-jun N-terminal kinase (JNK). Mol Endocrinol 2000;14(10):1592–602.

    Article  PubMed  CAS  Google Scholar 

  10. Acosta JJ, Munoz RM, Gonzalez L, Subtil-Rodriguez A, Dominguez-Caceres MA, Garcia-Martinez JM, et al. Src mediates prolactin-dependent proliferation of T47D and MCF7 cells via the activation of focal adhesion kinase/Erk1/2 and phosphatidylinositol 3-kinase pathways. Mol Endocrinol 2003;17(11):2268–82.

    Article  PubMed  CAS  Google Scholar 

  11. Miller SL, DeMaria JE, Freier DO, Riegel AM, Clevenger CV. Novel association of Vav2 and Nek3 modulates signaling through the human prolactin receptor. Mol Endocrinol 2005;19(4):939–49.

    Article  PubMed  CAS  Google Scholar 

  12. Miller SL, Antico G, Raghunath PN, Tomaszewski JE, Clevenger CV. Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells. Oncogene 2007;26(32):4668–78.

    Article  PubMed  CAS  Google Scholar 

  13. Kline JB, Moore DJ, Clevenger CV. Activation and association of the Tec tyrosine kinase with the human prolactin receptor: mapping of a Tec/Vav1-receptor binding site. Mol Endocrinol 2001;15(5):832–41.

    Article  PubMed  CAS  Google Scholar 

  14. Berlanga JJ, Gualillo O, Buteau H, Applanat M, Kelly PA, Edery M. Prolactin activates tyrosyl phosphorylation of insulin receptor substrate 1 and phosphatidylinositol-3-OH kinase. J Biol Chem 1997;272(4):2050–2.

    Article  PubMed  CAS  Google Scholar 

  15. Scotti ML, Langenheim JF, Tomblyn S, Springs AE, Chen WY. Additive effects of a prolactin receptor antagonist, G129R, and herceptin on inhibition of HER2-overexpressing breast cancer cells. Breast Cancer Res Treat. 2007; DOI 10.1007/s10549-007-9789-z.

  16. Tonko-Geymayer S, Goupille O, Tonko M, Soratroi C, Yoshimura A, Streuli C, et al. Regulation and function of the cytokine-inducible SH-2 domain proteins, CIS and SOCS3, in mammary epithelial cells. Mol Endocrinol 2002;16(7):1680–95.

    Article  PubMed  CAS  Google Scholar 

  17. Dif F, Saunier E, Demeneix B, Kelly PA, Edery M. Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor. Endocrinology 2001;142(12):5286–93.

    Article  PubMed  CAS  Google Scholar 

  18. Aoki N, Matsuda T. A nuclear protein tyrosine phosphatase TC-PTP is a potential negative regulator of the PRL-mediated signaling pathway: dephosphorylation and deactivation of signal transducer and activator of transcription 5a and 5b by TC-PTP in nucleus. Mol Endocrinol 2002;16(1):58–69.

    Article  PubMed  CAS  Google Scholar 

  19. Aoki N, Matsuda T. A cytosolic protein-tyrosine phosphatase PTP1B specifically dephosphorylates and deactivates prolactin-activated STAT5a and STAT5b. J Biol Chem 2000;275(50):39718–26.

    Article  PubMed  CAS  Google Scholar 

  20. Tomic S, Chughtai N, Ali S. SOCS-1, -2, -3: selective targets and functions downstream of the prolactin receptor. Mol Cell Endocrinol 1999;158(1–2):45–54.

    Article  PubMed  CAS  Google Scholar 

  21. Boutin JM, Edery M, Shirota M, Jolicoeur C, Lesueur L, Ali S, et al. Identification of a cDNA encoding a long form of prolactin receptor in human hepatoma and breast cancer cells. Mol Endocrinol 1989;3(9):1455–61.

    PubMed  CAS  Google Scholar 

  22. Somers W, Ultsch M, De Vos AM, Kossiakoff AA. The X-ray structure of a growth hormone-prolactin receptor complex. Nature 1994;372(6505):478–81.

    Article  PubMed  CAS  Google Scholar 

  23. Lebrun JJ, Ali S, Ullrich A, Kelly PA. Proline-rich sequence-mediated Jak2 association to the prolactin receptor is required but not sufficient for signal transduction. J Biol Chem 1995;270(18):10664–70.

    Article  PubMed  CAS  Google Scholar 

  24. Pezet A, Buteau H, Kelly PA, Edery M. The last proline of Box 1 is essential for association with JAK2 and functional activation of the prolactin receptor. Mol Cell Endocrinol 1997;129(2):199–208.

    Article  PubMed  CAS  Google Scholar 

  25. Pezet A, Ferrag F, Kelly PA, Edery M. Tyrosine docking sites of the rat prolactin receptor required for association and activation of stat5. J Biol Chem 1997;272(40):25043–50.

    Article  PubMed  CAS  Google Scholar 

  26. Ali S. Recruitment of the protein-tyrosine phosphatase SHP-2 to the C-terminal tyrosine of the prolactin receptor and to the adaptor protein Gab2. J Biol Chem 2000;275(50):39073–80.

    Article  PubMed  CAS  Google Scholar 

  27. Ali S, Nouhi Z, Chughtai N. SHP-2 regulates SOCS-1-mediated Janus kinase-2 ubiquitination/degradation downstream of the prolactin receptor. J Biol Chem 2003;278(52):52021–31.

    Article  PubMed  CAS  Google Scholar 

  28. Hu ZZ, Meng J, Dufau ML. Isolation and characterization of two novel forms of the human prolactin receptor generated by alternative splicing of a newly identified exon 11. J Biol Chem 2001;276(44):41086–94.

    Article  PubMed  CAS  Google Scholar 

  29. Kline JB, Roehrs H, Clevenger CV. Functional characterization of the intermediate isoform of the human prolactin receptor. J Biol Chem 1999;274(50):35461–8.

    Article  PubMed  CAS  Google Scholar 

  30. Clevenger CV, Chang WP, Ngo W, Pasha TL, Montone KT, Tomaszewski JE. Expression of prolactin and prolactin receptor in human breast carcinoma. Evidence for an autocrine/paracrine loop. Am J Pathol 1995;146(3):695–705.

    PubMed  CAS  Google Scholar 

  31. Chang WP, Ye Y, Clevenger CV. Stoichiometric structure-function analysis of the prolactin receptor signaling domain by receptor chimeras. Mol Cell Biol 1998;18(2):896–905.

    PubMed  CAS  Google Scholar 

  32. Trott JF, Hovey RC, Koduri S, Vonderhaar BK. Alternative splicing to exon 11 of human prolactin receptor gene results in multiple isoforms including a secreted prolactin-binding protein. J Mol Endocrinol 2003;30(1):31–47.

    Article  PubMed  CAS  Google Scholar 

  33. Qazi AM, Tsai-Morris CH, Dufau ML. Ligand-independent homo- and heterodimerization of human prolactin receptor variants: inhibitory action of the short forms by heterodimerization. Mol Endocrinol 2006;20(8):1912–23.

    Article  PubMed  CAS  Google Scholar 

  34. Tan D, Johnson DA, Wu W, Zeng L, Chen YH, Chen WY, et al. Unmodified prolactin (PRL) and S179D PRL-initiated bioluminescence resonance energy transfer between homo- and hetero-pairs of long and short human PRL receptors in living human cells. Mol Endocrinol 2005;19(5):1291–303.

    Article  PubMed  CAS  Google Scholar 

  35. Gadd SL, Clevenger CV. Ligand-independent dimerization of the human prolactin receptor isoforms: functional implications. Mol Endocrinol 2006;20(11):2734–46.

    Article  PubMed  CAS  Google Scholar 

  36. Kline JB, Rycyzyn MA, Clevenger CV. Characterization of a novel and functional human prolactin receptor isoform (deltaS1PRLr) containing only one extracellular fibronectin-like domain. Mol Endocrinol 2002;16(10):2310–22.

    Article  PubMed  CAS  Google Scholar 

  37. Kline JB, Clevenger CV. Identification and characterization of the prolactin-binding protein in human serum and milk. J Biol Chem 2001;276(27):24760–6.

    Article  PubMed  CAS  Google Scholar 

  38. Shiu RP. Prolactin receptors in human breast cancer cells in long-term tissue culture. Cancer Res 1979;39(11):4381–6.

    PubMed  CAS  Google Scholar 

  39. Peirce SK, Chen WY. Quantification of prolactin receptor mRNA in multiple human tissues and cancer cell lines by real time RT-PCR. J Endocrinol 2001;171(1):R1–4.

    Article  PubMed  CAS  Google Scholar 

  40. Touraine P, Martini JF, Zafrani B, Durand JC, Labaille F, Malet C, et al. Increased expression of prolactin receptor gene assessed by quantitative polymerase chain reaction in human breast tumors versus normal breast tissues. J Clin Endocrinol Metab 1998;83(2):667–74.

    Article  PubMed  CAS  Google Scholar 

  41. Laud K, Gourdou I, Belair L, Peyrat JP, Djiane J. Characterization and modulation of a prolactin receptor mRNA isoform in normal and tumoral human breast tissues. Int J Cancer 2000;85(6):771–6.

    Article  PubMed  CAS  Google Scholar 

  42. Reynolds C, Montone KT, Powell CM, Tomaszewski JE, Clevenger CV. Expression of prolactin and its receptor in human breast carcinoma. Endocrinology 1997;138(12):5555–60.

    Article  PubMed  CAS  Google Scholar 

  43. Gill S, Peston D, Vonderhaar BK, Shousha S. Expression of prolactin receptors in normal, benign, and malignant breast tissue: an immunohistological study. J Clin Pathol 2001;54(12):956–60.

    PubMed  CAS  Google Scholar 

  44. Meng J, Tsai-Morris CH, Dufau ML. Human prolactin receptor variants in breast cancer: low ratio of short forms to the long-form human prolactin receptor associated with mammary carcinoma. Cancer Res 2004;64(16):5677–82.

    Article  PubMed  CAS  Google Scholar 

  45. Ormandy CJ, Hall RE, Manning DL, Robertson JF, Blamey RW, Kelly PA, et al. Coexpression and cross-regulation of the prolactin receptor and sex steroid hormone receptors in breast cancer. J Clin Endocrinol Metab 1997;82(11):3692–9.

    Article  PubMed  CAS  Google Scholar 

  46. Leondires MP, Hu ZZ, Dong J, Tsai-Morris CH, Dufau ML. Estradiol stimulates expression of two human prolactin receptor isoforms with alternative exons-1 in T47D breast cancer cells. J Steroid Biochem Mol Biol 2002;82(2–3):263–8.

    Article  PubMed  CAS  Google Scholar 

  47. Hu ZZ, Zhuang L, Meng J, Tsai-Morris CH, Dufau ML. Complex 5′ genomic structure of the human prolactin receptor: multiple alternative exons 1 and promoter utilization. Endocrinology 2002;143(6):2139–42.

    Article  PubMed  CAS  Google Scholar 

  48. Hu ZZ, Zhuang L, Meng J, Leondires M, Dufau ML. The human prolactin receptor gene structure and alternative promoter utilization: the generic promoter hPIII and a novel human promoter hP(N). J Clin Endocrinol Metab 1999;84(3):1153–6.

    Article  PubMed  CAS  Google Scholar 

  49. Dong J, Tsai-Morris CH, Dufau ML. A novel estradiol/estrogen receptor alpha-dependent transcriptional mechanism controls expression of the human prolactin receptor. J Biol Chem 2006;281(27):18825–36.

    Article  PubMed  CAS  Google Scholar 

  50. Gutzman JH, Miller KK, Schuler LA. Endogenous human prolactin and not exogenous human prolactin induces estrogen receptor alpha and prolactin receptor expression and increases estrogen responsiveness in breast cancer cells. J Steroid Biochem Mol Biol 2004;88(1):69–77.

    Article  PubMed  CAS  Google Scholar 

  51. Liby K, Neltner B, Mohamet L, Menchen L, Ben-Jonathan N. Prolactin overexpression by MDA-MB-435 human breast cancer cells accelerates tumor growth. Breast Cancer Res Treat 2003;79(2):241–52.

    Article  PubMed  CAS  Google Scholar 

  52. Oakes SR, Robertson FG, Kench JG, Gardiner-Garden M, Wand MP, Green JE, et al. Loss of mammary epithelial prolactin receptor delays tumor formation by reducing cell proliferation in low-grade preinvasive lesions. Oncogene 2007;26(4):543–53.

    Article  PubMed  CAS  Google Scholar 

  53. de Castillo B, Cawthorn S, Moppett J, Shere M, Norman M. Expression of prolactin receptor mRNA in oestrogen receptor positive breast cancers pre- and post-tamoxifen therapy. Eur J Surg Oncol 2004;30(5):515–9.

    Article  PubMed  Google Scholar 

  54. De Petrocellis L, Melck D, Palmisano A, Bisogno T, Laezza C, Bifulco M, et al. The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation. Proc Natl Acad Sci U S A 1998;95(14):8375–80.

    Article  PubMed  Google Scholar 

  55. Melck D, Rueda D, Galve-Roperh I, De Petrocellis L, Guzman M, Di Marzo V. Involvement of the cAMP/protein kinase A pathway and of mitogen-activated protein kinase in the anti-proliferative effects of anandamide in human breast cancer cells. FEBS Lett 1999;463(3):235–40.

    Article  PubMed  CAS  Google Scholar 

  56. Melck D, De Petrocellis L, Orlando P, Bisogno T, Laezza C, Bifulco M, et al. Suppression of nerve growth factor Trk receptors and prolactin receptors by endocannabinoids leads to inhibition of human breast and prostate cancer cell proliferation. Endocrinology 2000;141(1):118–26.

    Article  PubMed  CAS  Google Scholar 

  57. Grimaldi C, Pisanti S, Laezza C, Malfitano AM, Santoro A, Vitale M, et al. Anandamide inhibits adhesion and migration of breast cancer cells. Exp Cell Res 2006;312(4):363–73.

    Article  PubMed  CAS  Google Scholar 

  58. Scorticati C, Mohn C, De Laurentiis A, Vissio P, Fernandez Solari J, Seilicovich A, et al. The effect of anandamide on prolactin secretion is modulated by estrogen. Proc Natl Acad Sci U S A 2003;100(4):2134–9.

    Article  PubMed  CAS  Google Scholar 

  59. Widschwendter M, Widschwendter A, Welte T, Daxenbichler G, Zeimet AG, Bergant A, et al. Retinoic acid modulates prolactin receptor expression and prolactin-induced STAT-5 activation in breast cancer cells in vitro. Br J Cancer 1999;79(2):204–10.

    PubMed  CAS  Google Scholar 

  60. Lu YF, Sun G, Wang X, Safe S. Inhibition of prolactin receptor gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin in MCF-7 human breast cancer cells. Arch Biochem Biophys 1996;332(1):35–40.

    Article  PubMed  CAS  Google Scholar 

  61. Buteau H, Pezet A, Ferrag F, Perrot-Applanat M, Kelly PA, Edery M. N-glycosylation of the prolactin receptor is not required for activation of gene transcription but is crucial for its cell surface targeting. Mol Endocrinol 1998;12(4):544–55.

    Article  PubMed  CAS  Google Scholar 

  62. Huang LJ, Constantinescu SN, Lodish HF. The N-terminal domain of Janus kinase 2 is required for Golgi processing and cell surface expression of erythropoietin receptor. Mol Cell 2001;8(6):1327–38.

    Article  PubMed  CAS  Google Scholar 

  63. He K, Loesch K, Cowan JW, Li X, Deng L, Wang X, et al. Janus kinase 2 enhances the stability of the mature growth hormone receptor. Endocrinology 2005;146(11):4755–65.

    Article  PubMed  CAS  Google Scholar 

  64. Royer Y, Staerk J, Costuleanu M, Courtoy PJ, Constantinescu SN. Janus kinases affect thrombopoietin receptor cell surface localization and stability. J Biol Chem 2005;280(29):27251–61.

    Article  PubMed  CAS  Google Scholar 

  65. Ragimbeau J, Dondi E, Alcover A, Eid P, Uze G, Pellegrini S. The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression. EMBO J 2003;22(3):537–47.

    Article  PubMed  CAS  Google Scholar 

  66. Mukhopadhyay D, Riezman H. Proteasome-independent functions of ubiquitin in endocytosis and signaling. Science 2007;315(5809):201–5.

    Article  PubMed  CAS  Google Scholar 

  67. Hicke L. Gettin' down with ubiquitin: turning off cell-surface receptors, transporters and channels. Trends Cell Biol 1999;9(3):107–12.

    Article  PubMed  CAS  Google Scholar 

  68. Djiane J, Houdebine LM, Kelly PA. Down-regulation of prolactin receptors in rabbit mammary gland: differential subcellular localization. Proc Soc Exp Biol Med 1981;168(3):378–81.

    PubMed  CAS  Google Scholar 

  69. Djiane J, Delouis C, Kelly PA. Prolactin receptor turnover in explants of pseudopregnant rabbit mammary gland. Mol Cell Endocrinol 1982;25(2):163–70.

    Article  PubMed  CAS  Google Scholar 

  70. Djiane J, Clauser H, Kelly PA. Rapid down-regulation of prolactin receptors in mammary gland and liver. Biochem Biophys Res Commun 1979;90(4):1371–8.

    Article  PubMed  CAS  Google Scholar 

  71. Genty N, Paly J, Edery M, Kelly PA, Djiane J, Salesse R. Endocytosis and degradation of prolactin and its receptor in Chinese hamster ovary cells stably transfected with prolactin receptor cDNA. Mol Cell Endocrinol 1994;99(2):221–8.

    Article  PubMed  CAS  Google Scholar 

  72. Li Y, Kumar KG, Tang W, Spiegelman VS, Fuchs SY. Negative regulation of prolactin receptor stability and signaling mediated by SCF(beta-TrCP) E3 ubiquitin ligase. Mol Cell Biol 2004;24(9):4038–48.

    Article  PubMed  CAS  Google Scholar 

  73. Li Y, Clevenger CV, Minkovsky N, Kumar KG, Raghunath PN, Tomaszewski JE, et al. Stabilization of prolactin receptor in breast cancer cells. Oncogene 2006;25(13):1896–902.

    Article  PubMed  CAS  Google Scholar 

  74. Lu JC, Piazza TM, Schuler LA. Proteasomes mediate prolactin-induced receptor down-regulation and fragment generation in breast cancer cells. J Biol Chem 2005;280(40):33909–16.

    Article  PubMed  CAS  Google Scholar 

  75. Bonifacino JS, Traub LM. Signals for sorting of transmembrane proteins to endosomes and lysosomes. Annu Rev Biochem 2003;72:395–447.

    Article  PubMed  CAS  Google Scholar 

  76. Thien CB, Langdon WY. Negative regulation of PTK signalling by Cbl proteins. Growth Factors 2005;23(2):161–7.

    Article  PubMed  CAS  Google Scholar 

  77. Thien CB, Langdon WY. c-Cbl and Cbl-b ubiquitin ligases: substrate diversity and the negative regulation of signalling responses. Biochem J 2005;391(Pt 2):153–66.

    PubMed  CAS  Google Scholar 

  78. Lu JC, Scott P, Strous GJ, Schuler LA. Multiple internalization motifs differentially used by prolactin receptor isoforms mediate similar endocytic pathways. Mol Endocrinol 2002;16(11):2515–27.

    Article  PubMed  CAS  Google Scholar 

  79. Vincent V, Goffin V, Rozakis-Adcock M, Mornon JP, Kelly PA. Identification of cytoplasmic motifs required for short prolactin receptor internalization. J Biol Chem 1997;272(11):7062–8.

    Article  PubMed  CAS  Google Scholar 

  80. Clague MJ, Urbe S. Endocytosis: the DUB version. Trends Cell Biol 2006;16(11):551–9.

    Article  PubMed  CAS  Google Scholar 

  81. Marijanovic Z, Ragimbeau J, Kumar KG, Fuchs SY, Pellegrini S. TYK2 activity promotes ligand-induced IFNAR1 proteolysis. Biochem J 2006;397(1):31–8.

    Article  PubMed  CAS  Google Scholar 

  82. Deng L, He K, Wang X, Yang N, Thangavel C, Jiang J, et al. Determinants of growth hormone receptor down-regulation. Mol Endocrinol 2007;21(7):1537–51.

    Article  PubMed  CAS  Google Scholar 

  83. Ahn S, Kim J, Lucaveche CL, Reedy MC, Luttrell LM, Lefkowitz RJ, et al. Src-dependent tyrosine phosphorylation regulates dynamin self-assembly and ligand-induced endocytosis of the epidermal growth factor receptor. J Biol Chem 2002;277(29):26642–51.

    Article  PubMed  CAS  Google Scholar 

  84. Frey MR, Dise RS, Edelblum KL, Polk DB. p38 kinase regulates epidermal growth factor receptor downregulation and cellular migration. EMBO J 2006;25(24):5683–92.

    Article  PubMed  CAS  Google Scholar 

  85. Zwang Y, Yarden Y. p38 MAP kinase mediates stress-induced internalization of EGFR: implications for cancer chemotherapy. EMBO J 2006;25(18):4195–206.

    Article  PubMed  CAS  Google Scholar 

  86. Walker AM. S179D prolactin: antagonistic agony. Mol Cell Endocrinol 2007;276(1–2):1–9.

    Article  PubMed  CAS  Google Scholar 

  87. Goffin V, Bernichtein S, Touraine P, Kelly PA. Development and potential clinical uses of human prolactin receptor antagonists. Endocr Rev 2005;26(3):400–22.

    Article  PubMed  CAS  Google Scholar 

  88. Beck MT, Chen NY, Franek KJ, Chen WY. Prolactin antagonist-endostatin fusion protein as a targeted dual-functional therapeutic agent for breast cancer. Cancer Res 2003;63(13):3598–604.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Work in the Fuchs lab is supported by the Susan G. Komen Breast Cancer Foundation Grant BCTR0504447 (to S.Y.F.) and NCI grant CA115281 (to S.Y.F.).

Author information

Authors and Affiliations

  1. Department of Animal Biology and Mari Lowe Center for Comparative Oncology Research, University of Pennsylvania, Philadelphia, PA, 19104, USA

    G. Swaminathan, B. Varghese & S. Y. Fuchs

  2. Cell and Molecular Biology Program, Biomedical Graduate School, University of Pennsylvania, Philadelphia, PA, 19104, USA

    B. Varghese

  3. Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 380 S. University Avenue, Hill 316, Philadelphia, PA, 19104, USA

    S. Y. Fuchs

Authors
  1. G. Swaminathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Varghese
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Y. Fuchs
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Y. Fuchs.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Swaminathan, G., Varghese, B. & Fuchs, S.Y. Regulation of Prolactin Receptor Levels and Activity in Breast Cancer. J Mammary Gland Biol Neoplasia 13, 81–91 (2008). https://doi.org/10.1007/s10911-008-9068-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10911-008-9068-6

Keywords

Search

Navigation