Protein 4.1B expression is induced in mammary epithelial cells during pregnancy and regulates their proliferation
Protein 4.1B expression is induced in mammary epithelial cells during pregnancy and regulates their proliferation
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DOI：
10.1038/sj.onc.1208813
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发表时间：
2005-09-01
期刊：
影响因子：
8
通讯作者：
Sherman, LS
中科院分区：
文献类型：
--
作者：
Kuns, R;Kissil, JL;Sherman, LS
4.1B是连接跨膜蛋白与肌动蛋白细胞骨架的蛋白质4.1超家族的成员。4.1B基因定位于染色体18p11.3，在乳腺肿瘤中发生杂合性丢失。在这里，我们研究了4.1B在小鼠乳腺上皮细胞的表达，发现4.1B是显着上调乳腺上皮细胞在怀孕期间，当有广泛的细胞增殖。相比之下，4.1B不表达在处女，泌乳，或退化的乳腺上皮。为了检测4.1B缺失对乳腺上皮细胞增殖的影响，我们分析了4.1B缺失小鼠的乳腺。4.1B缺失导致妊娠期间乳腺上皮细胞增殖显著增加，但对处女或退化小鼠的乳腺上皮细胞增殖没有影响。此外，我们发现4.1B通过诱导G（1）细胞周期阻滞抑制乳腺上皮细胞系的增殖，其特征在于细胞周期蛋白A表达降低和Rb磷酸化降低，并伴有erbB2磷酸化降低。这种细胞周期阻滞不涉及MAPK、JNK或Akt活性的改变。总的来说，我们的研究结果表明，4.1B调节乳腺上皮细胞增殖在怀孕期间，并建议其损失可能会影响乳腺癌的发病机制，在经产妇女。
4.1B is a member of the protein 4.1 superfamily of proteins that link transmembrane proteins to the actin cytoskeleton. The 4.1B gene localizes to chromosome 18p11.3, which undergoes loss of heterozygosity in mammary tumors. Here, we examine the expression of 4.1B in murine mammary epithelium and find that 4.1B is dramatically upregulated in mammary epithelial cells during pregnancy when there is extensive cell proliferation. In contrast, 4.1B is not expressed in virgin, lactating, or involuting mammary epithelium. To examine the consequence of 4.1B loss on mammary epithelial cell proliferation, we analysed mammary glands in 4.1B-null mice. 4.1B loss results in a significant increase in mammary epithelial cell proliferation during pregnancy, but has no effect on mammary epithelial cell proliferation, in virgin or involuting mice. Furthermore, we show that 4.1B inhibits the proliferation of mammary epithelial cell lines by inducing a G(1) cell cycle arrest, characterized by decreased cyclin A expression and reduced Rb phosphorylation, and accompanied by reduced erbB2 phosphorylation. This cell cycle arrest does not involve alterations in the activities of MAPK, JNK, or Akt. Collectively, our findings demonstrate that 4.1B regulates mammary epithelial cell proliferation during pregnancy and suggest that its loss may influence mammary carcinoma pathogenesis in multiparous women.