p16 通过与乳腺癌细胞中的 HIF-1alpha 相互作用来调节 VEGF 的表达。
p16 Modulates VEGF expression via its interaction with HIF-1alpha in breast cancer cells.
机构信息
Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
出版信息
Cancer Invest. 2010 Jul;28(6):588-97. doi: 10.3109/07357900903286941.
Abstract
The degree of tumor progression (such as growth, angiogenesis, and metastasis) directly correlates with the expression of vascular endothelial growth factor (VEGF), but inversely correlates with the expression of tumor-suppressor gene p16, therefore we examined whether the restoration of p16 in breast cancer cells would modulate VEGF expression. Adenoviral-mediated p16 expression downregulated VEGF gene expression in breast cancer cells, and inhibited breast cancer cell-induced angiogenesis by a dorsal air sac model in mice. Moreover, p16 appears to form a complex with HIF-1a, the transcription factor for the VEGF gene promoter. Taken together, the binding between p16 and HIF-1a protein may alter HIF-1a's ability to transactivate VEGF expression.
摘要
肿瘤的进展程度（如生长、血管生成和转移）与血管内皮生长因子（VEGF）的表达直接相关，但与肿瘤抑制基因 p16 的表达呈负相关，因此我们研究了乳腺癌细胞中 p16 的恢复是否会调节 VEGF 的表达。腺病毒介导的 p16 表达下调了乳腺癌细胞中 VEGF 基因的表达，并通过小鼠背部气囊模型抑制了乳腺癌细胞诱导的血管生成。此外，p16 似乎与 HIF-1a 形成复合物，HIF-1a 是 VEGF 基因启动子的转录因子。综上所述，p16 和 HIF-1a 蛋白之间的结合可能改变 HIF-1a 激活 VEGF 表达的能力。
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