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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Overexpression of LM04 induces mammary hyperplasia, promotes cell invasion, and is a predictor of poor outcome in breast cancer
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Overexpression of LM04 induces mammary hyperplasia, promotes cell invasion, and is a predictor of poor outcome in breast cancer

机译：LM04的过表达诱导乳腺增生，促进细胞侵袭，并预示着乳腺癌预后不良

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摘要

The zinc finger protein LMO4 is overexpressed in a high proportion of breast carcinomas. Here, we report that overexpression of a mouse mammary tumor virus (MMTV)-Lmo4 transgene in the mouse mammary gland elicits hyperplasia and mammary intraepi-thelial neoplasia or adenosquamous carcinoma in two transgenic strains with a tumor latency of 13-18 months. To investigate cellular processes controlled by L.MO4 and those that may be deregulated during oncogenesis, we used RNA interference. Down-regulation of LMO4 expression reduced proliferation of human breast cancer cells and increased differentiation of mouse mammary epithelial cells. Furthermore, small-interfering-RNA-transfected breast cancer cells (MDA-MB-231) had a reduced capacity to migrate and invade an extracellular matrix. Conversely, overexpression of LMO4 in noninvasive, immortalized human MCF10A cells promoted cell motility and invasion. Significantly, in a cohort of 159 primary breast cancers, high nuclear levels of LMO4 were an independent predictor of death from breast cancer. Together, these findings suggest that deregulation of LMO4 in breast epithelium contributes directly to breast neoplasia by altering the rate of cellular proliferation and promoting cell invasion.
机译：锌指蛋白LMO4在高比例的乳腺癌中过表达。在这里，我们报告小鼠乳腺中的小鼠乳腺肿瘤病毒（MMTV）-Lmo4转基因的过表达引起了两种潜伏期为13-18个月的转基因菌株中的增生和乳腺上皮内瘤样变或腺鳞癌。为了研究由L.MO4控制的细胞过程以及在肿瘤发生过程中可能被失控的细胞过程，我们使用了RNA干扰。 LMO4表达的下调减少了人类乳腺癌细胞的增殖并增加了小鼠乳腺上皮细胞的分化。此外，小干扰RNA转染的乳腺癌细胞（MDA-MB-231）迁移和侵袭细胞外基质的能力降低。相反，在无创，永生化的人MCF10A细胞中LMO4的过表达促进细胞运动和侵袭。值得注意的是，在159个原发性乳腺癌队列中，LMO4的高核水平是乳腺癌死亡的独立预测因子。总之，这些发现表明，乳腺上皮中LMO4的失调通过改变细胞增殖速率和促进细胞侵袭而直接导致乳腺肿瘤。

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