Vav3 oncogene is involved in regulation of secretory phospholipase A2-IIa expression in prostate cancer
Vav3 oncogene is involved in regulation of secretory phospholipase A2-IIa expression in prostate cancer
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DOI：
10.3892/or.2011.1237
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发表时间：
2011-06-01
期刊：
影响因子：
4.2
通讯作者：
Lu, Shan
中科院分区：
文献类型：
--
作者：
Dong, Zhongyun;Liu, Yin;Lu, Shan
我们之前的研究发现，相对于雄激素依赖性前列腺癌细胞，Vav/3癌基因和分泌磷脂酶A2-IIa （sPLA2-IIa）在雄激素非依赖性前列腺癌细胞中过表达，并参与激素难治性前列腺癌的发展。Vav3是一种具有信号分子和辅激活因子活性的多功能蛋白。sPLA2-IIa是HER/HER2-PI3K-Akt-NE-kappa B信号的下游效应因子，参与炎症反应和肿瘤发生。本研究的目的是确定Vav3是否参与sPLA2-IIa表达的上调，因为Vav3信号在HER/ her2介导的通路中。在46例前列腺癌标本中，Vav3和sPLA2-IIa分别在48%和83%的人类前列腺癌中过表达。Vav3过表达与sPLA2-IIa的高水平表达显著相关。此外，在两个前列腺癌标本中观察到显著的Vav3核定位，支持前列腺癌细胞中的共激活子活性。进一步分析发现，Vav3通过HER/HER2-PI3K-Akt-NF-kappa B信号在转录水平上调sPLA2-IIa基因的表达。这些数据表明，Vav3过表达是前列腺癌中sPLA2-IIa表达升高的另一个潜在机制。
Our previous study revealed that Vav/3 oncogene and secretory phospholipase A2-IIa (sPLA2-IIa) are overexpressed in androgen-independent prostate cancer cells relative to their androgen-dependent counterparts and contribute to development of hormone refractory prostate cancer. Vav3 is a multiple function protein with both signaling molecule and coactivator activities. sPLA2-IIa is a downstream effector of HER/HER2-PI3K-Akt-NE-kappa B signaling and involved in inflammatory response and tumorigenesis. The aim of the current study was to determine whether Vav3 is involved in up-regulation of sPLA2-IIa expression, given that Vav3 signals in the HER/HER2-elicited pathway. Among 46 prostate cancer specimens examined, Vav3 and sPLA2-IIa are overexpressed in 48 and 83% human prostate cancers, respectively. Vav3 overexpression is significantly associated with a high level expression of sPLA2-IIa. In addition, significant Vav3 nuclear localization is observed in two prostate cancer specimens, supporting a coactivator activity in prostate cancer cells. Further analysis revealed that Vav3 up-regulates expression of the sPLA2-IIa gene at the transcriptional level via HER/HER2-PI3K-Akt-NF-kappa B signaling. These data revealed that Vav3 overexpression as an additional underlying mechanism contributes to elevated sPLA2-IIa expression in prostate cancer.