Cowin Pamela, Rowlands Tracey M, Hatsell Sarah J
Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA.
Curr Opin Cell Biol. 2005 Oct;17(5):499-508. doi: 10.1016/j.ceb.2005.08.014.
Recent studies show that cadherins and catenins are hormonally regulated and carry out physiological roles during mammary development but have pathological effects when deregulated. E-cadherin expression is irreversibly lost in invasive lobular breast cancer (ILC). Animal models of ILC provide mechanistic insight, confirming that E-cadherin serves as both a tumor suppressor and an invasion suppressor in ILC. Ductal breast cancer involves complex, reversible, epigenetic modulation of multiple cadherins. Transcriptional regulators of E-cadherin have been identified that induce epithelial-to-mesenchymal transitions. Catenins are lost or mislocalized in tumors lacking cadherins. However, beta-catenin signaling is upregulated by numerous pathways in >50% of breast tumors and animal models suggest its oncogenic function in breast relates to its role in mammary progenitor cell expansion.
近期研究表明,钙黏蛋白和连环蛋白受激素调节,在乳腺发育过程中发挥生理作用,但失调时会产生病理影响。在浸润性小叶乳腺癌(ILC)中,E-钙黏蛋白的表达会不可逆地丧失。ILC的动物模型提供了机制性见解,证实E-钙黏蛋白在ILC中既是肿瘤抑制因子又是侵袭抑制因子。导管乳腺癌涉及多种钙黏蛋白复杂、可逆的表观遗传调控。已鉴定出诱导上皮-间质转化的E-钙黏蛋白转录调节因子。在缺乏钙黏蛋白的肿瘤中,连环蛋白会丢失或定位错误。然而,在超过50%的乳腺肿瘤中,β-连环蛋白信号通过多种途径上调,动物模型表明其在乳腺中的致癌功能与其在乳腺祖细胞扩增中的作用有关。