Paige Laboratory, Department of Veterinary and Animal Sciences, University of Massachusetts, 161 Holdsworth Way, Amherst, MA 01003-9286, USA.
Cell Mol Life Sci. 2010 Apr;67(7):1017-23. doi: 10.1007/s00018-009-0244-7.
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.
卵巢激素在促进和预防乳腺癌方面的矛盾作用已经争论了 30 多年。遗传研究表明,卵巢激素通过 NF-κB 发挥作用,刺激增殖和导管伸长,而 p53 肿瘤抑制蛋白在使乳腺上皮抵抗肿瘤形成方面起着核心作用。转录谱表明,卵巢激素刺激一系列与 NF-κB 和 p53 相互作用的基因,以裁决增殖和监测的竞争需求。参与染色质重塑的基因是雌激素和孕激素的急性转录反应之一。这些基因被认为启动了影响增殖和监测之间平衡的表观遗传程序,并使乳腺上皮抵抗肿瘤。