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KLF6 通过 c-Src 介导的途径抑制乳腺癌中雌激素受体介导的细胞生长。

KLF6 inhibits estrogen receptor-mediated cell growth in breast cancer via a c-Src-mediated pathway.

机构信息

Department of General Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, China.

出版信息

Mol Cell Biochem. 2010 Feb;335(1-2):29-35. doi: 10.1007/s11010-009-0237-8. Epub 2009 Aug 26.

Abstract

Estrogen receptors play a key role in breast cancer development and progression. Kruppel-like factor 6 (KLF6) is a tumour-suppressing protein. The aim of this study was to identify the role of KLF6 inhibition in estrogen receptor(alpha) (ERalpha)-elicited breast cancer development. Protein expression levels were examined by western blot analysis and immunoprecipitation was used to analyse interactions between proteins. An MTT assay was used to study cell proliferation. We found that KLF6 mediates cell growth in ERalpha-positive breast cancer cells through interaction with the c-Src protein. This interaction causes inactivation of the Erk and Akt proteins. These pathways are critical for the proliferation and survival of breast cancer cells. We also established that KLF6 could not mediate cell growth in ERalpha-negative cells. We conclude that KLF6 can modulate ERalpha-mediated cell growth in breast cancer cells. The unique role of KLF6 in mediating cell growth in breast cancer cells opens up the possibility of a new therapeutic strategy for treating breast cancer.

摘要

雌激素受体在乳腺癌的发生和发展中起着关键作用。Kruppel 样因子 6(KLF6)是一种肿瘤抑制蛋白。本研究旨在鉴定 KLF6 抑制在雌激素受体(alpha)(ERalpha)引发的乳腺癌发展中的作用。通过 Western blot 分析检测蛋白表达水平,并用免疫沉淀分析蛋白质之间的相互作用。MTT 法用于研究细胞增殖。我们发现 KLF6 通过与 c-Src 蛋白相互作用介导 ERalpha 阳性乳腺癌细胞的生长。这种相互作用导致 Erk 和 Akt 蛋白失活。这些通路对乳腺癌细胞的增殖和存活至关重要。我们还确定 KLF6 不能介导 ERalpha 阴性细胞的细胞生长。我们的结论是,KLF6 可以调节 ERalpha 介导的乳腺癌细胞的细胞生长。KLF6 在介导乳腺癌细胞生长中的独特作用为治疗乳腺癌开辟了新的治疗策略的可能性。

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