Suppression of breast cancer metastasis through the inhibition of VEGF-mediated tumor angiogenesis.
Suppression of breast cancer metastasis through the inhibition of VEGF-mediated tumor angiogenesis.
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发表时间：
2007
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通讯作者：
Jun Zhang;A. Lu;D. Beech;Bing-Hua Jiang;Yi Lu
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作者：
Jun Zhang;A. Lu;D. Beech;Bing-Hua Jiang;Yi Lu
乳腺癌治疗失败的主要原因之一是发生转移，即原发肿瘤向远处器官扩散。因此，在转移过程的关键阶段进行干预，如血管生成，对于有效治疗乳腺癌是很重要的。血管内皮生长因子（VEGF）在肿瘤血管生成中起着关键作用。由于肿瘤的恶性程度与VEGF的表达直接相关，而与肿瘤抑制基因p16的表达呈负相关，因此我们研究了在缺乏p16表达的乳腺癌细胞中恢复p16是否会调节VEGF的表达，如果是，p16的表达对肿瘤血管生成和转移的影响如何。为了促进p16的表达，我们利用表达p16的重组腺病毒（AdRSVp16）转染乳腺癌细胞株MDA-MB-231和JygMC(a)。本研究表明，腺病毒介导的p16表达下调乳腺癌细胞中VEGF基因的表达，抑制乳腺癌细胞诱导的血管生成，抑制小鼠乳腺肿瘤自发转移模型的转移。此外，我们还研究了p16调控VEGF表达的机制。
One of the major causes of failure in the treatment of breast cancer is the occurrence of metastasis, the spreading of the primary tumor to distant organs. It is thus important to intervene at a key step of metastatic process, such as angiogenesis, for effective breast cancer treatment. Vascular endothelial growth factor (VEGF) plays a pivotal role in tumor angiogenesis. Because degree of tumor malignancy directly correlates with the expression of VEGF but inversely correlates with the expression of tumor suppressor gene p16, we examined whether restoration of p16 in breast cancer cells that lack p16 expression would modulate VEGF expression, and if so, how are the effects of p16 expression on tumor angiogenesis and metastasis. To facilitate induction of p16 expression, a recombinant adenovirus expressing p16 (AdRSVp16) was used to transduce breast cancer cell lines MDA-MB-231 and JygMC(A). This study showed that adenoviral-mediated p16 expression downregulated VEGF gene expression in breast cancer cells, inhibited breast cancer cell-induced angiogenesis, and suppressed breast tumor metastasis in a spontaneous metastasis model in mice. Moreover, the mechanism of how p16 regulates VEGF expression is also investigated.