Delta N89 beta-catenin induces precocious development, differentiation, and neoplasia in mammary gland.

Delta N89 beta-catenin induces precocious development, differentiation, and neoplasia in mammary gland.
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DOI:
10.1083/jcb.153.3.555
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发表时间:
2001-04-30
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Cowin P
Cowin P
中科院分区:
其他
文献类型:
--
作者:
Imbert A;Eelkema R;Jordan S;Feiner H;Cowin P

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为了研究β-catenin在乳腺发育和肿瘤形成中的作用,我们表达了一种稳定的、转录活性形式的β-catenin,其缺乏NH 2末端89个氨基酸(ΔN89β-catenin),受小鼠乳腺肿瘤病毒长末端重复序列控制。我们的结果表明,ΔN89β-连环蛋白诱导雄性和雌性小鼠乳腺的早熟小叶肺泡发育和分化。原始ΔN89β-catenin乳腺类似于野生型(wt)妊娠小鼠中发现的乳腺,并且不适当地表达细胞周期蛋白D1 mRNA。与野生型乳腺相反,野生型乳腺在停止哺乳后恢复处女外观,转基因乳腺逐渐进入中期妊娠状态。所有转基因雌性在生命早期发展为多发性侵袭性腺癌。令人惊讶的是,ΔN89β-catenin表型与该腺体中Wnt基因过表达引起的表型不同。特别地,ΔN89β-连环蛋白对导管侧分支没有影响。这表明Wnt诱导导管分支涉及额外的下游效应物或调节物。
To investigate the role of β-catenin in mammary gland development and neoplasia, we expressed a stabilized, transcriptionally active form of β-catenin lacking the NH2-terminal 89 amino acids (ΔN89β-catenin) under the control of the mouse mammary tumor virus long terminal repeat. Our results show that ΔN89β-catenin induces precocious lobuloalveolar development and differentiation in the mammary glands of both male and female mice. Virgin ΔN89β-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 ΔN89β-catenin phenotype differs from those elicited by overexpression of Wnt genes in this gland. In particular, ΔN89β-catenin has no effect on ductal side branching. This suggests that Wnt induction of ductal branching involves additional downstream effectors or modulators.
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