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Effects of raf kinase inhibitor protein expression on metastasis and progression of human breast cancer.

机译:raf激酶抑制剂蛋白表达对人乳腺癌转移和进展的影响。

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Raf kinase inhibitor protein (RKIP) has been shown to be a metastasis suppressor in many kinds of malignant tumors. But its function in breast cancer was not yet clarified completely. We detected RKIP expression in clinical samples of primary breast cancer, breast cancer metastases, and in different breast cancer cells. Compared with the normal breast epithelia, benign breast epithelia, or in situ ductal carcinoma, the expression level of RKIP is decreased in invasive carcinoma and significantly reduced or lost in the metastasis lymph node matched to the invasive carcinoma. To explore the potential role of RKIP in breast cancer metastasis, we studied the effect of RKIP on the malignant phenotypes of the breast cancer cells with ectopically overexpression or knockdown of RKIP. Cell proliferation, soft-agar colony formation, in vitro adhesion assay, invasion, and migation assays were done to examine the malignant phenotypes of the transfected cells. Consequently, RKIP has no effect on in vitro proliferation rate or colony-forming ability of MDA-MB-435 cells. In vitro cell invasion and migration assays indicated that the RKIP expression was inversely associated with the invasiveness of MDA-MB-435 cells. Consistent with these results, in the orthotopic murine models, we observed that overexpression of RKIP in breast cancer cells impaired invasiveness and metastasis, whereas down-regulation of RKIP expression promoted invasiveness and metastasis. These results indicate that RKIP is a metastasis suppressor gene of human breast cancer.
机译:Raf激酶抑制剂蛋白(RKIP)已被证明是多种恶性肿瘤中的转移抑制因子。但是其在乳腺癌中的功能尚未完全阐明。我们在原发性乳腺癌,乳腺癌转移瘤和不同乳腺癌细胞的临床样品中检测到RKIP表达。与正常乳腺上皮细胞,良性乳腺上皮细胞或原位导管癌相比,浸润性癌中RKIP的表达水平降低,而与浸润性癌匹配的转移淋巴结中RKIP的表达水平明显降低或丧失。为了探讨RKIP在乳腺癌转移中的潜在作用,我们研究了RKIP对乳腺癌细胞异位过表达或敲低的恶性表型的影响。进行细胞增殖,软琼脂集落形成,体外粘附测定,侵袭和迁移测定以检查转染细胞的恶性表型。因此,RKIP对MDA-MB-435细胞的体外增殖速率或集落形成能力没有影响。体外细胞侵袭和迁移试验表明,RKIP表达与MDA-MB-435细胞的侵袭力呈负相关。与这些结果一致,在原位鼠模型中,我们观察到乳腺癌细胞中RKIP的过表达损害了浸润和转移,而RKIP表达的下调促进了浸润和转移。这些结果表明RKIP是人乳腺癌的转移抑制基因。

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