Estrogens, regulation of p53 and breast cancer risk: a balancing act.
The paradoxical effects of ovarian hormones in both the promotion and prevention of breast cancer have been debated for over 30 years. Genetic studies have demonstrated that ovarian hormones act through NF-kappaB to stimulate proliferation and ductal elongation, whereas the p53 tumor suppressor protein plays a central role in rendering the mammary epithelium resistant to tumorigenesis. Transcriptional profiles now suggest that ovarian hormones stimulate a constellation of genes that interact with NF-kappaB and p53 to arbitrate the competing demands for proliferation and surveillance. Genes that participate in chromatin remodeling are among the acute transcriptional responses to estrogens and progestins. These genes are proposed to initiate epigenetic programs that influence the balance between proliferation and surveillance, and render the breast epithelium resistant to tumors.
Jerry
D Joseph
DJ
Paige Laboratory, Department of Veterinary and Animal Sciences, University of Massachusetts, 161 Holdsworth Way, Amherst, MA 01003-9286, USA. jjerry@vasci.umass.edu
Dunphy
Karen A
KA
Hagen
Mary J
MJ
D001943:Breast Neoplasms / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly; D044127:Epigenesis, Genetic; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D004967:Estrogens; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53