HIF-1α通过下调TP53INP1促进乳腺癌细胞的迁移及侵袭

HIF-1αpromotes migration and invasion of breast cancer cells by down-regulating TP53INP1

目的:探讨HIF-1α通过调节TP53INP1蛋白对乳腺癌细胞迁移及侵袭能力的影响。方法:通过免疫组化检测60例乳腺癌标本中TP53INP1和HIF-1α的表达情况及分析其临床病理资料。通过体外构建HIF-1α及共转染HIF-1α和TP53INP1细胞模型,迁移侵袭实验和划痕实验检测HIF-1α和TP53INP1对乳腺癌细胞迁移侵袭能力的影响;Western blot实验研究共同下调HIF-1α和TP53INP1对MMP2、VEGF蛋白表达水平的影响。结果:免疫组化实验显示HIF-1α在人乳腺癌组织中高表达,TP53INP1呈低表达,两者之间具有相关性且均与淋巴结转移有关(P<0.05)。迁移侵袭实验及划痕实验显示在乳腺癌MDA-MB-231细胞和MCF-7细胞中下调HIF-1α抑制了迁移侵袭及愈合能力,MCF-7细胞中共同转染下调HIF-1α和TP53INP1质粒之后逆转了乳腺癌细胞的迁移侵袭能力及愈合能力(P<0.05)。Western blot实验显示shHIF-1α和TP53INP1共转染后在MDA-MB-231细胞中MMP2表达水平高于下调HIF-1α表达组。共转染shHIF-1α和shTP53INP1质粒后在MCF-7细胞中,VEGF和MMP2表达高于下调shHIF-1α组(P<0.05)。结论:HIF-1α可能通过下调TP53INP1的表达促进乳腺癌细胞的迁移侵袭能力。

Objective:To investigate the effect that HIF-1αon breast cancer cells migration and invasion by the regulation of TP53INP1.Methods:Immunohistochemistry staining showed the expression of TP53INP1 and HIF-1αin 60 breast cancer patients tissues and the clinicopathological data were analyzed.Wound-healing assay,invasion and migration assay confirmed the influence of breast cancer migration and invasion on interaction between TP53INP1 and HIF-1α.The expression of MMP2,VEGF related protein markers were tested by Western blot in cotransfected shHIF-1 and TP53INP1 or shTP53INP1 breast cancer cells.Results:The expression of HIF-1αwas high and TP53INP1 was low in breast cancer tissues and there is association between HIF-1αand TP53INP1.Furthermore,HIF-1αand TP53INP1 expression were correlated with lymph node metastasis(P<0.05).Downregulation of HIF-1αcould inhibit the ability of breast cancer cells migration and invasion,however,cotransfected shHIF-1αand shTP53INP1 MCF-7 cells reversed the ability of breast cancer cells migration and invasion(P<0.05).Western blot results showed that the expression of MMP2 was high in cotransfected shHIF-1αand TP53INP1 MDA-MB-231 cells,the expression of VEGF and MMP2 were high in cotransfected shHIF-1αand shTP53INP1 MCF-7 cells(P<0.05).Conclusion:HIF-1αpromote ability of breast cancer cells migration and invasion by the downregulation of TP53INP1.