Advertisement

Breast Cancer Research and Treatment

, Volume 133, Issue 2, pp 617–634 | Cite as

Life stage differences in mammary gland gene expression profile in non-human primates

  • Petra Stute
  • Sonja Sielker
  • Charles E. Wood
  • Thomas C. Register
  • Cynthia J. Lees
  • Fitriya N. Dewi
  • J. Koudy Williams
  • Janice D. Wagner
  • Ulrich Stefenelli
  • J. Mark Cline
Preclinical study

Abstract

Breast cancer (BC) is the most common malignancy of women in the developed world. To better understand its pathogenesis, knowledge of normal breast development is crucial, as BC is the result of disregulation of physiologic processes. The aim of this study was to investigate the impact of reproductive life stages on the transcriptional profile of the mammary gland in a primate model. Comparative transcriptomic analyses were carried out using breast tissues from 28 female cynomolgus macaques (Macaca fascicularis) at the following life stages: prepubertal (n = 5), adolescent (n = 4), adult luteal (n = 5), pregnant (n = 6), lactating (n = 3), and postmenopausal (n = 5). Mammary gland RNA was hybridized to Affymetrix GeneChip® Rhesus Macaque Genome Arrays. Differential gene expression was analyzed using ANOVA and cluster analysis. Hierarchical cluster analysis revealed distinct separation of life stage groups. More than 2,225 differentially expressed mRNAs were identified. Gene families or pathways that changed across life stages included those related to estrogen and androgen (ESR1, PGR, TFF1, GREB1, AR, 17HSDB2, 17HSDB7, STS, HSD11B1, AKR1C4), prolactin (PRLR, ELF5, STAT5, CSN1S1), insulin-like growth factor signaling (IGF1, IGFBP1, IGFBP5), extracellular matrix (POSTN, TGFB1, COL5A2, COL12A1, FOXC1, LAMC1, PDGFRA, TGFB2), and differentiation (CD24, CD29, CD44, CD61, ALDH1, BRCA1, FOXA1, POSTN, DICER1, LIG4, KLF4, NOTCH2, RIF1, BMPR1A, TGFB2). Pregnancy and lactation displayed distinct patterns of gene expression. ESR1 and IGF1 were significantly higher in the adolescent compared to the adult animals, whereas differentiation pathways were overrepresented in adult animals and pregnancy-associated life stages. Few individual genes were distinctly different in postmenopausal animals. Our data demonstrate characteristic patterns of gene expression during breast development. Several of the pathways activated during pubertal development have been implicated in cancer development and metastasis, supporting the idea that other developmental markers may have application as biomarkers for BC.

Keywords

Breast development Gene microarray Breast cancer Stem cell Estrogen Progesterone 

Abbreviations

AKR1C4

Aldo-keto reductase family 1, member C4

AKT1

v-akt Murine thymoma viral oncogene homolog 1

ALDH1

Aldehyde dehydrogenase 1 family, member A1

AR

Androgen receptor

BC

Breast cancer

BMPR1A

Bone morphogenetic protein receptor, type 1A

BRCA1

Breast cancer 1

CAP

Cyclase-associated protein

CD24, CD29, CD44, CD61

Cluster designation antigens 24, 29, 44, and 61

CENPA

Centromeric protein A

COL12A1

Collagen, type XII, alpha-1

COL5A2

Collagen, type V, alpha-2

CSN1S1

Casein alpha S1

DICER1

Dicer 1, ribonuclease type III

ELF5

E74-like factor 5

ERα

Estrogen receptor alpha (protein)

ERβ

Estrogen receptor beta (protein)

ESR1

Estrogen receptor alpha (gene)

ESR2

Estrogen receptor beta (gene)

FOXA1

Forkhead box A1

FOXC1

Forkhead box C1

GATA3

Glutamyl-tRNA amidotransferase subunit A binding protein 3

GH

Growth hormone

GREB1

Gene regulated by estrogen in breast cancer 1

GTM3

Glutathione s-transferase mu 3

HSD11B1

11-beta-hydroxysteroid dehydrogenase type 1

HSD17B2

17-beta-hydroxysteroid dehydrogenase type 2

HSD17B7

17-beta-hydroxysteroid dehydrogenase type 7

IGF1

Insulin-like growth factor 1

IGFBP1

Insulin-like growth factor–binding protein 1

IGFBP5

Insulin-like growth factor–binding protein 5

IGHG1

IgG heavy-chain locus

Jak2

Janus kinase 2

KLF4

Kruppel-like factor 4

LAMC1

Laminin, gamma-1

LIG4

DNA ligase IV

LRRN3

Leucine-rich repeat protein, neuronal, 3

MKI67

Proliferation-related antigen Ki67

NEK10

Never in mitosis gene a–related kinase 10

NOTCH2

Notch gene homolog 2

PCA

Principal components analysis

PDGFRA

Platelet-derived growth factor receptor, alpha

PECI

Peroxisomal D3,D2-enoyl-CoA isomerase

PGR

Progesterone receptor

PGRB

Progesterone receptor B

POSTN

Periostin

PPM1K

Protein phosphatase, PP2C domain-containing, 1K

PRLR

Prolactin receptor

RANKL

Receptor activator of NF-kappa-B ligand

RIF1

RAP1 interacting factor homolog

SERF1A

Small EDRK-rich factor 1A

STAT5

Signal transducer and activator of transcription 5

STS

Steroid sulfatase

SULT

Sulfotransferase

TFF1

Trefoil factor 1

TGFB1

Transforming growth factor, beta-1

TGFB2

Transforming growth factor, beta-2

TGFB3

Transforming growth factor, beta-3

WNT5B

Wingless-related MMTV integration site 5B

Notes

Acknowledgments

The authors are grateful for the technical support of Ms. Hermina Borgerink, Ms. Jean Gardin, Ms. Lisa O’Donnell, and Mr. Joseph Finley and also for the work of students Ms. Sara Dillon, Ms. Amelia Hubbard, and Mr. Russell O’Donnell. This study has been supported by the German Research Foundation Grants STU 469/2-1 and STU 469/3-1 (to PS), a German Society of Obstetrics and Gynecology Grant (to PS), and National Institutes of Health Grants R01 AT00639-06 (to JMC), RO3 AG18170 (to TCR), R01 R01AG017864 (to JKW), and P40 RR 021380 (to JDW).

References

  1. 1.
    Monaghan P, Perusinghe NP, Cowen P, Gusterson BA (1990) Peripubertal human breast development. Anat Rec 226:501–508PubMedCrossRefGoogle Scholar
  2. 2.
    Russo J, Hu YF, Yang X, Russo IH (2000) Developmental, cellular, and molecular basis of human breast cancer. J Natl Cancer Inst Monogr 27:17–37PubMedCrossRefGoogle Scholar
  3. 3.
    Hovey RC, Trott JF (2004) Morphogenesis of mammary gland development. Adv Exp Med Biol 554:219–228PubMedGoogle Scholar
  4. 4.
    Hens JR, Wysolmerski JJ (2005) Key stages of mammary gland development: molecular mechanisms involved in the formation of the embryonic mammary gland. Breast Cancer Res 7:220–224PubMedCrossRefGoogle Scholar
  5. 5.
    Sternlicht MD, Kouros-Mehr H, Lu P, Werb Z (2006) Hormonal and local control of mammary branching morphogenesis. Differentiation 74:365–381PubMedCrossRefGoogle Scholar
  6. 6.
    LaMarca HL, Rosen JM (2008) Minireview: hormones and mammary cell fate—what will I become when I grow up? Endocrinology 149:4317–4321PubMedCrossRefGoogle Scholar
  7. 7.
    Booth BW, Boulanger CA, Smith GH (2007) Alveolar progenitor cells develop in mouse mammary glands independent of pregnancy and lactation. J Cell Physiol 212:729–736PubMedCrossRefGoogle Scholar
  8. 8.
    Wagner KU, Boulanger CA, Henry MD, Sgagias M, Hennighausen L, Smith GH (2002) An adjunct mammary epithelial cell population in parous females: its role in functional adaptation and tissue renewal. Development 129:1377–1386PubMedGoogle Scholar
  9. 9.
    Hilakivi-Clarke L (2007) Nutritional modulation of terminal end buds: its relevance to breast cancer prevention. Curr Cancer Drug Targets 7:465–474PubMedCrossRefGoogle Scholar
  10. 10.
    Molyneux G, Regan J, Smalley MJ (2007) Mammary stem cells and breast cancer. Cell Mol Life Sci 64:3248–3260PubMedCrossRefGoogle Scholar
  11. 11.
    Lacroix M (2006) Significance, detection and markers of disseminated breast cancer cells. Endocr Relat Cancer 13:1033–1067PubMedCrossRefGoogle Scholar
  12. 12.
    Magness CL, Fellin PC, Thomas MJ, Korth MJ, Agy MB, Proll SC, Fitzgibbon M, Scherer CA, Miner DG, Katze MG, Iadonato SP (2005) Analysis of the Macaca mulatta transcriptome and the sequence divergence between Macaca and human. Genome Biol 6:R60PubMedCrossRefGoogle Scholar
  13. 13.
    Cline JM, Soderqvist G, von Schoultz B, Skoog L (1997) Regional distribution of proliferating cells and hormone receptors in the mammary gland of surgically postmenopausal macaques. Gynecol Obstet Invest 44:41–46PubMedCrossRefGoogle Scholar
  14. 14.
    Cline JM, Wood CE (2008) The mammary glands of macaques. Toxicol Pathol 36:130S–141SCrossRefGoogle Scholar
  15. 15.
    Stute P, Wood CE, Kaplan JR, Cline JM (2004) Cyclic changes in the mammary gland of cynomolgus macaques. Fertil Steril 82:1160S–1170SCrossRefGoogle Scholar
  16. 16.
    Wood CE, Hester JM, Cline JM (2007) Mammary gland development in early pubertal female macaques. Toxicol Pathol 35(6):795–805PubMedCrossRefGoogle Scholar
  17. 17.
    Cline JM (2007) Assessing the mammary gland of nonhuman primates: effects of endogenous hormones and exogenous hormonal agents and growth factors. Birth Defects Res B Dev Reprod Toxicol 80:126–146PubMedCrossRefGoogle Scholar
  18. 18.
    Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Statist Soc Ser B M1 57:289–300Google Scholar
  19. 19.
    Reiner A, Yekutieli D, Benjamini Y (2003) Identifying differentially expressed genes using false discovery rate controlling procedures. Bioinformatics 19:368–375PubMedCrossRefGoogle Scholar
  20. 20.
    van ‘t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530–536PubMedCrossRefGoogle Scholar
  21. 21.
    Ghosh G, Thompson DA, Weigel RJ (2000) PDZK1 and GREB1 are estrogen-regulated genes expressed in hormone-responsive breast cancer. Cancer Res 60:6367–6375PubMedGoogle Scholar
  22. 22.
    Amiry N, Kong X, Muniraj N, Kannan N, Grandison PM, Lin J, Yang Y, Vouyovitch CM, Borges S, Perry JK, Mertani HC, Zhu T, Liu D, Lobie PE (2009) Trefoil factor-1 (TFF1) enhances oncogenicity of mammary carcinoma cells. Endocrinology 150(10):4473–4483PubMedCrossRefGoogle Scholar
  23. 23.
    Mathelin C, Tomasetto C, Rio MC (2005) Trefoil factor 1 (pS2/TFF1), a peptide with numerous functions. Bull Cancer 92:773–781PubMedGoogle Scholar
  24. 24.
    Conneely OM, Mulac-Jericevic B, Lydon JP (2003) Progesterone-dependent regulation of female reproductive activity by two distinct progesterone receptor isoforms. Steroids 68:771–778PubMedCrossRefGoogle Scholar
  25. 25.
    Mulac-Jericevic B, Lydon JP, DeMayo FJ, Conneely OM (2003) Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform. PNAS 100:9744–9749PubMedCrossRefGoogle Scholar
  26. 26.
    Buck K, Vanek M, Groner B, Ball RK (1992) Multiple forms of prolactin receptor messenger ribonucleic acid are specifically expressed and regulated in murine tissues and the mammary cell line HC11. Endocrinology 130:1108–1114PubMedCrossRefGoogle Scholar
  27. 27.
    Clarke LA, Wathes DC, Jabbour HN (1997) Expression and localization of prolactin receptor messenger ribonucleic acid in red deer ovary during the estrous cycle and pregnancy. Biol Reprod 57:865–872PubMedCrossRefGoogle Scholar
  28. 28.
    Freeman ME, Kanyicska B, Lerant A, Nagy G (2000) Prolactin: structure, function, and regulation of secretion. Physiol Rev 80:1523–1631PubMedGoogle Scholar
  29. 29.
    Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA (1998) Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev 19:225–268PubMedCrossRefGoogle Scholar
  30. 30.
    Gouilleux F, Wakao H, Mundt M, Groner B (1994) Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription. EMBO J 13:4361–4369PubMedGoogle Scholar
  31. 31.
    Liu X, Robinson GW, Gouilleux F, Groner B, Hennighausen L (1995) Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue. PNAS 92:8831–8835PubMedCrossRefGoogle Scholar
  32. 32.
    Erwin RA, Kirken RA, Malabarba MG, Farrar WL, Rui H (1995) Prolactin activates Ras via signaling proteins SHC, growth factor receptor bound 2, and son of sevenless. Endocrinology 136:3512–3518PubMedCrossRefGoogle Scholar
  33. 33.
    Das R, Vonderhaar BK (1996) Activation of raf-1, MEK and MAP kinase in prolactin responsive mammary cells. Breast Cancer Res Treat 40:141–149PubMedCrossRefGoogle Scholar
  34. 34.
    Piccoletti R, Bendinelli P, Maroni P (1997) Signal transduction pathway of prolactin in rat liver. Mol Cell Endocrinol 135:169–177PubMedCrossRefGoogle Scholar
  35. 35.
    Fresno Vara JA, Caceres MA, Silva A, Martin-Perez J (2001) Src family kinases are required for prolactin induction of cell proliferation. Mol Biol Cell 12(7):2171–2183PubMedGoogle Scholar
  36. 36.
    Tessier C, Prigent-Tessier A, Ferguson-Gottschall S, Gu Y, Gibori G (2001) PRL antiapoptotic effect in the rat decidua involves the PI3 K/protein kinase B-mediated inhibition of caspase-3 activity. Endocrinology 142(9):4086–4094PubMedCrossRefGoogle Scholar
  37. 37.
    Oakes SR, Rogers RL, Naylor MJ, Ormandy CJ (2008) Prolactin regulation of mammary gland development. J Mammary Gland Biol Neoplasia 13:13–28PubMedCrossRefGoogle Scholar
  38. 38.
    Neville MC, McFadden TB, Forsyth I (2002) Hormonal regulation of mammary differentiation and milk secretion. J Mammary Gland Biol Neoplasia 7:49–66PubMedCrossRefGoogle Scholar
  39. 39.
    Zhou J, Ng S, Adesanya-Famuiya O, Anderson K, Bondy CA (2000) Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression. FASEB J 14:1725–1730PubMedCrossRefGoogle Scholar
  40. 40.
    Dimitrakakis C, Zhou J, Wang J, Belanger A, LaBrie F, Cheng C, Powell D, Bondy C (2003) A physiologic role for testosterone in limiting estrogenic stimulation of the breast. Menopause 10:292–298PubMedCrossRefGoogle Scholar
  41. 41.
    Park S, Koo J, Park HS, Kim JH, Choi SY, Lee JH, Park BW, Lee KS (2010) Expression of androgen receptors in primary breast cancer. Ann Oncol 21:488–492Google Scholar
  42. 42.
    Vihko P, Herrala A, Härkönen P, Isomaa V, Kaija H, Kurkela R, Pulkka A (2006) Control of cell proliferation by steroids: the role of 17HSDs. Mol Cell Endocrinol 248:141–148PubMedCrossRefGoogle Scholar
  43. 43.
    Chetrite GS, Cortes-Prieto J, Philippe JC, Wright F, Pasqualini JR (2000) Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. J Steroid Biochem Mol Biol 72:23–27PubMedCrossRefGoogle Scholar
  44. 44.
    Oakes SR, Naylor MJ, Asselin-Labat ML, Blazek KD, Gardiner-Garden M, Hilton HN, Kazlauskas M, Pritchard MA, Chodosh LA, Pfeffer PL, Lindeman GJ, Visvader JE, Ormandy CJ (2008) The Ets transcription factor Elf5 specifies mammary alveolar cell fate. Genes Dev 22:581–586PubMedCrossRefGoogle Scholar
  45. 45.
    Liu S, Ginestier C, Charafe-Jauffret E, Foco H, Kleer CG, Merajver SD, Dontu G, Wicha MS (2008) BRCA1 regulates human mammary stem/progenitor cell fate. Proc Natl Acad Sci USA 105:1680–1685Google Scholar
  46. 46.
    Grelier G, Voirin N, Ay AS, Cox DG, Chabaud S, Treilleux I, Léon-Goddard S, Rimokh R, Mikaelian I, Venoux C, Puisieux A, Lasset C, Moyret-Lalle C (2009) Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype. Br J Cancer 101:673–683PubMedCrossRefGoogle Scholar
  47. 47.
    Chen W, Wang S, Tian T, Bai J, Hu Z, Xu Y, Dong J, Chen F, Wang X, Shen H (2009) Phenotypes and genotypes of insulin-like growth factor 1, IGF-binding protein-3 and cancer risk: evidence from 96 studies. Eur J Hum Genet 17:1668–1675PubMedCrossRefGoogle Scholar
  48. 48.
    Foster KW, Frost AR, McKie-Bell P, Lin CY, Engler JA, Grizzle WE, Ruppert JM (2000) Increase of GKLF messenger RNA and protein expression during progression of breast cancer. Cancer Res 60:6488–6495PubMedGoogle Scholar
  49. 49.
    Miller KA, Eklund EA, Peddinghaus ML, Cao Z, Fernandes N, Turk PW, Thimmapaya B, Weitzman SA (2001) Kruppel-like factor 4 regulates laminin alpha 3A expression in mammary epithelial cells. Journal of Biological Chemistry 276:42863–42868PubMedCrossRefGoogle Scholar
  50. 50.
    Pandya AY, Talley LI, Frost AR, Fitzgerald TJ, Trivedi V, Chakravarthy M, Chhieng DC, Grizzle WE, Engler JA, Krontiras H, Bland KI, LoBuglio AF, Lobo-Ruppert SM, Ruppert JM (2004) Nuclear localization of KLF4 is associated with an aggressive phenotype in early-stage breast cancer. Clin Cancer Res 10:2709–2719PubMedCrossRefGoogle Scholar
  51. 51.
    Tan SH, Nevalainen MT (2008) Signal transducer and activator of transcription 5A/B in prostate and breast cancers. Endocr Relat Cancer 15:367–390PubMedCrossRefGoogle Scholar
  52. 52.
    Figueroa JD, Flanders KC, Garcia-Closas M, Anderson WF, Yang XR, Matsuno RK, Duggan MA, Pfeiffer RM, Ooshima A, Cornelison R, Gierach GL, Brinton LA, Lissowska J, Peplonska B, Wakefield LM, Sherman ME (2009) Expression of TGF-beta signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics. Breast Cancer Res Treat 121:727–735Google Scholar
  53. 53.
    García-Closas M, Egan KM, Newcomb PA, Brinton LA, Titus-Ernstoff L, Chanock S, Welch R, Lissowska J, Peplonska B, Szeszenia-Dabrowska N, Zatonski W, Bardin-Mikolajczak A, Struewing JP (2006) Polymorphisms in DNA double-strand break repair genes and risk of breast cancer: two population-based studies in USA and Poland, and meta-analyses. Hum Genet 119:376–788PubMedCrossRefGoogle Scholar
  54. 54.
    Jakubowska A, Gronwald J, Menkiszak J, Górski B, Huzarski T, Byrski T, Tołoczko-Grabarek A, Gilbert M, Edler L, Zapatka M, Eils R, Lubiński J, Scott RJ, Hamann U (2010) BRCA1-associated breast and ovarian cancer risks in Poland: no association with commonly studied polymorphisms. Breast Cancer Res Treat 119:201–211PubMedCrossRefGoogle Scholar
  55. 55.
    Kuschel B, Auranen A, McBride S, Novik KL, Antoniou A, Lipscombe JM, Day NE, Easton DF, Ponder BA, Pharoah PD, Dunning A (2002) Variants in DNA double-strand break repair genes and breast cancer susceptibility. Hum Mol Genet 11:1399–1407PubMedCrossRefGoogle Scholar
  56. 56.
    Howarth KD, Blood KA, Ng BL, Beavis JC, Chua Y, Cooke SL, Raby S, Ichimura K, Collins VP, Carter NP, Edwards PA (2007) Array painting reveals a high frequency of balanced translocations in breast cancer cell lines that break in cancer-relevant genes. Oncogene 27:3345–3359PubMedCrossRefGoogle Scholar
  57. 57.
    Ademuyiwa FO, Thorat MA, Jain RK, Nakshatri H, Badve S (2010) Expression of Forkhead-box protein A1, a marker of luminal A type breast cancer, parallels low Oncotype DX 21-gene recurrence scores. Mod Pathol 23:270–275PubMedCrossRefGoogle Scholar
  58. 58.
    Ahmed S, Thomas G, Ghoussaini M et al (2009) Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2. Nat Genet 41:585–590PubMedCrossRefGoogle Scholar
  59. 59.
    Lee SH, Jeong EG, Yoo NJ, Lee SH (2007) Mutational analysis of NOTCH1, 2, 3 and 4 genes in common solid cancers and acute leukemias. APMIS 115:1357–1363PubMedCrossRefGoogle Scholar
  60. 60.
    Kabbage M, Chahed K, Hamrita B, Guillier CL, Trimeche M, Remadi S, Hoebeke J, Chouchane L (2008) Protein alterations in infiltrating ductal carcinomas of the breast as detected by nonequilibrium pH gradient electrophoresis and mass spectrometry. J Biomed Biotechnol 2008:564127PubMedCrossRefGoogle Scholar
  61. 61.
    He J, Pan Y, Hu J, Albarracin C, Wu Y, Dai JL (2007) Profile of Ets gene expression in human breast carcinoma. Cancer Biol Ther 6:76–82PubMedCrossRefGoogle Scholar
  62. 62.
    Yan W, Cao QJ, Arenas RB, Bentley B, Shao R (2010) GATA3 inhibits breast cancer metastasis through the reversal of epithelial-mesenchymal transition. J Biol Chem 285:14042–14051Google Scholar
  63. 63.
    Sasaki H, Yu CY, Dai M, Tam C, Loda M, Auclair D, Chen LB, Elias A (2003) Elevated serum periostin levels in patients with bone metastases from breast but not lung cancer. Breast Cancer Res Treat 77(3):245–252PubMedCrossRefGoogle Scholar
  64. 64.
    Pearson WR, Vorachek WR, Xu SJ, Berger R, Hart I, Vannais D, Patterson D (1993) Identification of class-mu glutathione transferase genes GSTM1-GSTM5 on human chromosome 1p13. Am J Hum Genet 53:220–233PubMedGoogle Scholar
  65. 65.
    Geisbrecht BV, Zhang D, Schulz H, Gould SJ (1999) Characterization of PECI, a novel monofunctional delta-3, delta-2-enoyl-CoA isomerase of mammalian peroxisomes. J Biol Chem 274:21797–21803PubMedCrossRefGoogle Scholar
  66. 66.
    Cleveland DW, Mao Y, Sullivan KF (2003) Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling. Cell 112:407–421PubMedCrossRefGoogle Scholar
  67. 67.
    Rudolph MC, McManaman JL, Hunter L, Phang T, Neville MC (2003) Functional development of the mammary gland: use of expression profiling and trajectory clustering to reveal changes in gene expression during pregnancy, lactation, and involution. J Mammary Gland Biol Neoplasia 8(3):287–307PubMedCrossRefGoogle Scholar
  68. 68.
    Lemay DG, Neville MC, Rudolph MC, Pollard KS, German JB (2007) Gene regulatory networks in lactation: identification of global principles using bioinformatics. BMC Syst Biol 1:56PubMedCrossRefGoogle Scholar
  69. 69.
    Zhao H, Huang M, Chen Q, Wang Q, Pan Y (2011) Comparative gene expression analysis in mouse models for identifying critical pathways in mammary gland development. Breast Cancer Res Treat [Epub ahead of print]Google Scholar
  70. 70.
    Anderson SM, Rudolph MC, McManaman JL, Neville MC (2007) Key stages in mammary gland development. Secretory activation in the mammary gland: it’s not just about milk protein synthesis! Breast Cancer Res 9(1):204PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Petra Stute
    • 1
  • Sonja Sielker
    • 2
  • Charles E. Wood
    • 3
  • Thomas C. Register
    • 3
  • Cynthia J. Lees
    • 3
  • Fitriya N. Dewi
    • 3
  • J. Koudy Williams
    • 3
  • Janice D. Wagner
    • 3
  • Ulrich Stefenelli
    • 4
  • J. Mark Cline
    • 3
  1. 1.Department of Gynecologic Endocrinology and Reproductive MedicineUniversity Women’s HospitalBerneSwitzerland
  2. 2.Arrows Biomedical Deutschland GmbHMunsterGermany
  3. 3.Department of Pathology/Section on Comparative MedicineWake Forest University School of MedicineWinston-SalemUSA
  4. 4.Services-In-StatisticsWürzburgGermany

Personalised recommendations