Chromatin Remodeling and Pregnancy-Induced Differentiation
Breast cancer is the most frequently diagnosed cancer in postmenopausal women and the leading cause of cancer death in females worldwide . The global incidence of breast cancer has gradually increased over the last few decades [1, 2]. Although the reasons of this increase are uncertain, it is known that the breast cancer risk is reduced in women who gave birth to a child before age 24  a reduction that is enhanced by breast-feeding and multiparity [4, 5]. Experimentally it has been demonstrated that the protection conferred by pregnancy is mediated by the differentiation of the breast, a physiological process driven by the complex hormonal milieu created by the placenta and the fetus [6–8]. The postulate that the degree of differentiation acquired through an early pregnancy changes the genomic signature that differentiates the lobular structures of early parous (P) women from those of nulliparous (NP) women has been demonstrated through the enriched analysis of the genomic profile of breasts of parous and nulliparous postmenopausal and premenopausal women [9, 10] and of rodent models [6–8, 11, 12]. These findings have allowed researchers to demonstrate that significant differences in the expression of genes controlling differentiation and transcription exist between groups that differ in their parity history. These data explain at molecular level the basis of the protective effect of pregnancy and establishes a functional genomic signature of breast cancer risk reduction, confirming a postulate published in 1997 .
KeywordsMammary Gland Breast Cancer Risk Chromatin Remodel Nulliparous Woman Parous Woman
We, the authors, acknowledge the contributions of the many members of the Breast Cancer Research Laboratory at the Fox Chase Cancer Center, especially Drs. Y Su, R. Lopez, and F. Sheriff, who have worked with us to generate the data described in Sect. 7.8 incorporated into this chapter and allowed us to elaborate it into a unified concept.
- 5.Yang XR, Chang-Claude J, Goode EL, Couch FJ, Nevanlinna H, Milne RL, Gaudet M, Schmidt MK, Broeks A, Cox A, Fasching PA, Hein R et al (2011) Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst 103:250–263PubMedCrossRefGoogle Scholar
- 8.Russo J, Russo IH (eds) (2004) Molecular basis of breast cancer: prevention and treatment. Springer, Berlin, p 447Google Scholar
- 13.Belitskaya-Levy I, Zeleniuch-Jacquotte A, Russo J, Russo IH, Bordas P, Ahman J, Afanasyeva Y, Johansson R, Lenner P, Li X, de Cicco-Lopez RL, Peri S, Ross E, Russo PA, Santucci-Pereira J, Sheriff FS, Slifker M, Hallmans G, Toniolo P, Arslan AA (2011) Characterization of a genomic signature of pregnancy identified in the breast. Cancer Prev Res 4:1457–1464CrossRefGoogle Scholar
- 27.Kubicek S, Schotta G, Lachner M, Sengupta R, Kohlmaier A, Perez-Burgos L, Linderson Y, Martens JH, O’Sullivan RJ, Fodor BD, Yonezawa M, Peters AH, Jenuwein T (2006) The role of histone modifications in epigenetic transitions during normal and perturbed development. Ernst Schering Res Found Workshop 57:1–27PubMedCrossRefGoogle Scholar
- 30.Erwin JA, Lee JT (2010) Characterization of X-chromosome inactivation status in human pluripotent stem cells. Curr Protoc Stem Cell Biol Chapter 1:Unit 1B.6Google Scholar
- 33.Lee J (2010) Characterization of X-chromosome inactivation status in human pluripotent stem cells. Curr Protoc Stem Cell Biol Chapter 1:Unit 1B.6Google Scholar
- 40.Kobayashi T, Ishida J, Musashi M, Ota S, Yoshida T, Shimizu Y, Chuma M, Kawakami H, Asaka M, Tanaka J, Imamura M, Kobayashi M, Itoh H, Edamatsu H, Sutherland LC, Brachmann RK (2011) p53 transactivation is involved in the antiproliferative activity of the putative tumor suppressor RBM5. Int J Cancer 128:304–318PubMedCrossRefGoogle Scholar
- 41.Salomonis N, Schlieve CR, Pereira L, Wahlquist C, Colas A, Zambon AC, Vranizan K, Spindler MJ, Pico AR, Cline MS, Clark TA, Williams A, Blume JE, Samal E, Mercola M, Merrill BJ, Conklin BR (2010) Alternative splicing regulates mouse embryonic stem cell pluripotency and differentiation. Proc Natl Acad Sci U S A 107:10514–10519PubMedCrossRefGoogle Scholar
- 46.Russo J, Balogh GA, Chen J, Fernandez SV, Fernbaugh R, Heulings R, Mailo DA, Moral R, Russo PA, Sheriff F, Vanegas JE, Wang R, Russo IH (2006) The concept of stem cell in the mammary gland and its implication in morphogenesis, cancer and prevention. Front Biosci 11:151–172PubMedCrossRefGoogle Scholar
- 51.Russo J, Santucci-Pereira J, López de Cicco R, Sheriff F, Russo PA, Peri S, Slifker M, Ross E, Mello MLS, Vidal BC, Belitskaya-Lévy I, Arslan A, Zeleniuch-Jacquotte A, Bordas P, Lenner P, Ahman J, Afanasyeva Y, Hallmans G, Toniolo P, Russo IH (2012) Pregnancy-induced chromatin remodeling in the breast of postmenopausal women. Int J Cancer 131(5):1059–1070. doi: 10.1002/ijc.27323 PubMedCrossRefGoogle Scholar
- 59.Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5:R80PubMedCrossRefGoogle Scholar