Wnt proteins in mammary development and cancer
Wnt proteins in mammary development and cancer
复制标题
DOI：
10.1023/b:jomg.0000037157.94207.33
复制
发表时间：
2004-04-01
影响因子：
2.5
通讯作者：
Brown, AMC
中科院分区：
文献类型：
--
作者：
Brennan, KR;Brown, AMC
Wnt家族的分泌蛋白在胚胎发育的调节中发挥着广泛的作用，而Wnt/β-catenin途径的异常激活是人类癌症中最常见的信号异常之一。虽然WRIT信号在发育中的后果在细胞水平上是不同的，但它们通常与细胞命运的决定有关。最近的数据还表明，Wnt蛋白影响某些组织中的干细胞19的自我更新。在乳腺中，WRIT信号与乳房雏形的初始发育以及妊娠期间发生的导管分支和肺泡形态发生密切相关。WNT1或WNT10b在小鼠乳腺中的转基因表达导致小叶肺泡增生，并有发展为癌症的主要风险。最近的证据表明，这种表型与多能祖细胞群体的扩张有关。在人类乳腺癌中，β-连环蛋白积聚的证据表明，规范的Wnt信号通路在超过50%的癌症中是活跃的。然而，可能导致这种信号激活的特定突变尚未确定。
Secreted proteins of the Wnt family play widespread roles in the regulation of embryonic development, and aberrant activation of the canonical Wnt/beta-catenin pathway is one of the most frequent signaling abnormalities known in human cancer. While the consequences of Writ signaling in development are diverse at the cellular level, they are often concerned with cell fate determination. Recent data also indicate that Wnt proteins influence the self-renewal of stem 19 cells in certain tissues. In the mammary gland, Writ signals are strongly implicated in initial development of the mammary rudiments, and in the ductal branching and alveolar morphogenesis that occurs during pregnancy. Transgenic expression of Wnt1 or Wnt10b in the mouse mammary gland leads to lobuloalveolar hyperplasia with a major risk of progression to carcinoma. Recent evidence suggests that this phenotype is associated with expansion of a multipotent progenitor cell population. In human breast cancer, evidence of beta-catenin accumulation implies that the canonical Wnt signaling pathway is active in over 50% of carcinomas. However, specific mutations that might account for this activation of signaling have not yet been identified.