Imbert A, Eelkema R, Jordan S, Feiner H, Cowin P
Department of Cell Biology, New York University Medical School, New York, New York 10016, USA.
J Cell Biol. 2001 Apr 30;153(3):555-68. doi: 10.1083/jcb.153.3.555.
To investigate the role of beta-catenin in mammary gland development and neoplasia, we expressed a stabilized, transcriptionally active form of beta-catenin lacking the NH(2)-terminal 89 amino acids (Delta N 89 beta-catenin) under the control of the mouse mammary tumor virus long terminal repeat. Our results show that Delta N 89 beta-catenin induces precocious lobuloalveolar development and differentiation in the mammary glands of both male and female mice. Virgin Delta N 89 beta-catenin mammary glands resemble those found in wild-type (wt) pregnant mice and inappropriately express cyclin D1 mRNA. In contrast to wt mammary glands, which resume a virgin appearance after cessation of lactation, transgenic mammary glands involute to a midpregnant status. All transgenic females develop multiple aggressive adenocarcinomas early in life. Surprisingly, the Delta N89 beta-catenin phenotype differs from those elicited by overexpression of Wnt genes in this gland. In particular, Delta N 89 beta-catenin has no effect on ductal side branching. This suggests that Wnt induction of ductal branching involves additional downstream effectors or modulators.
为了研究β-连环蛋白在乳腺发育和肿瘤形成中的作用，我们在小鼠乳腺肿瘤病毒长末端重复序列的控制下，表达了一种稳定的、缺乏氨基末端89个氨基酸的转录活性形式的β-连环蛋白（ΔN 89β-连环蛋白）。我们的结果表明，ΔN 89β-连环蛋白在雄性和雌性小鼠的乳腺中诱导早熟的小叶腺泡发育和分化。未生育的ΔN 89β-连环蛋白乳腺类似于野生型（wt）怀孕小鼠的乳腺，并且不恰当地表达细胞周期蛋白D1 mRNA。与wt乳腺在停止哺乳后恢复未生育状态不同，转基因乳腺退化到怀孕中期状态。所有转基因雌性小鼠在生命早期都会发生多个侵袭性腺癌。令人惊讶的是，ΔN89β-连环蛋白表型与该腺体中Wnt基因过表达所引发的表型不同。特别是，ΔN 89β-连环蛋白对导管侧支没有影响。这表明Wnt诱导导管分支涉及额外的下游效应器或调节剂。
