TGF-β Biology in Mammary Development and Breast Cancer
TGF-β Biology in Mammary Development and Breast Cancer
复制标题
DOI：
10.1101/cshperspect.a003277
复制
发表时间：
2011-01-01
影响因子：
7.2
通讯作者：
Barcellos-Hoff, Mary Helen
中科院分区：
文献类型：
--
作者：
Moses, Harold;Barcellos-Hoff, Mary Helen
Daniel和Silberstein于1987年首次发现转化生长因子- β 1 （tgf - β）与乳腺上皮细胞发育有关，Lippman及其同事于1988年发现转化生长因子- β 1与乳腺癌细胞和激素抵抗有关。tgf - β通过特异性调节上皮细胞增殖、凋亡和细胞外基质，对乳腺形态发生和分泌功能至关重要。tgf - β对不同细胞类型的不同作用因多种水平的调控和环境对细胞反应的影响而复杂化。使用控制表达和条件缺失小鼠模型的研究强调了tgf - β生物学在乳腺发育和分化周期中的复杂性。乳腺癌中tgf - β生长调节的早期缺失演变为介导细胞相互作用和表型驱动侵袭性疾病的根本失调。两个突出的问题是了解原位生物控制机制和肿瘤进展中tgf - β调节被破坏的情况。
Transforming growth factor-beta 1 (TGF-beta) was first implicated in mammary epithelial development by Daniel and Silberstein in 1987 and in breast cancer cells and hormone resistance by Lippman and colleagues in 1988. TGF-beta is critically important for mammary morphogenesis and secretory function through specific regulation of epithelial proliferation, apoptosis, and extracellular matrix. Differential TGF-beta effects on distinct cell types are compounded by regulation at multiple levels and the influence of context on cellular responses. Studies using controlled expression and conditional-deletion mouse models underscore the complexity of TGF-beta biology across the cycle of mammary development and differentiation. Early loss of TGF-beta growth regulation in breast cancer evolves into fundamental deregulation that mediates cell interactions and phenotypes driving invasive disease. Two outstanding issues are to understand the mechanisms of biological control in situ and the circumstances by which TGF-beta regulation is subverted in neoplastic progression.