FAS expression inversely correlates with PTEN level in prostate cancer and a PI 3-kinase inhibitor synergizes with FAS siRNA to induce apoptosis
FAS expression inversely correlates with PTEN level in prostate cancer and a PI 3-kinase inhibitor synergizes with FAS siRNA to induce apoptosis
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DOI：
10.1038/sj.onc.1208555
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发表时间：
2005-08-11
期刊：
影响因子：
8
通讯作者：
Watabe, K
中科院分区：
文献类型：
--
作者：
Bandyopadhyay, S;Pai, SK;Watabe, K
脂肪酸合成酶(Fas)是脂肪酸生物合成途径中的一个关键酶，已被证明在各种类型的人类癌症中过表达，因此被认为是抗癌治疗的一个有吸引力的靶点。然而，Fas基因在肿瘤细胞中过度表达的确切机制尚不清楚。在这篇报道中，我们证明了抑癌基因PTEN的表达与临床上前列腺癌Fas的表达呈显著负相关，体外抑制PTEN基因会导致Fas的过度表达。我们还发现，这两个基因的联合表达状态是一个比单独使用其中一个基因更好的预后标志物。此外，我们的结果表明，siRNA对Fas基因的特异性抑制导致了前列腺癌细胞的凋亡，抑制PI3K途径与Fas siRNA协同作用，促进了肿瘤细胞的死亡。这些结果为探索PTEN信号通路抑制剂与Fas siRNA联合使用来抑制前列腺癌生长提供了强有力的理论基础。
Fatty acid synthase (FAS), a key enzyme of the fatty acid biosynthetic pathway, has been shown to be overexpressed in various types of human cancer and is, therefore, considered to be an attractive target for anticancer therapy. However, the exact mechanism of overexpression of the FAS gene in tumor cells is not well understood. In this report, we demonstrate that the expression of the tumor suppressor gene PTEN has a significant inverse correlation with FAS expression in the case of prostate cancer in the clinical setting, and inhibition of the PTEN gene leads to the overexpression of FAS in vitro. We also found that the combination of the expression status of these two genes is a better prognostic marker than either gene alone. Furthermore, our results indicate that the specific inhibition of FAS gene by siRNA leads to apoptosis of prostate tumor cells, and inhibition of PI 3-kinase pathway synergizes with FAS siRNA to enhance tumor cell death. These results provide a strong rationale for exploring the therapeutic use of an inhibitor of the PTEN signaling pathway in conjunction with the FAS siRNA to inhibit prostate tumor growth.