肝细胞生长因子通过使胃癌细胞中的BAD磷酸化来促进细胞存活。

Hepatocyte growth factor promotes cell survival by phosphorylation of BAD in gastric cancer cells.

作者信息

Lee Kyung Hee, Choi Eun Young, Kim Min Kyoung, Hyun Myung Soo, Eun Jong Ryul, Jang Byung Ik, Kim Tae Nyeun, Kim Sang Woon, Song Sun Kyo, Kim Jung Hye, Kim Jae-Ryong

机构信息

Department of Hematology-Oncology, College of Medicine, Yeungnam University, Daegu, Korea.

出版信息

Oncol Res. 2008;17(1):23-32. doi: 10.3727/096504008784046072.

DOI:10.3727/096504008784046072

PMID:18488712

Abstract

Hepatocyte growth factor (HGF) is one of the survival factors with a potent ability to promote cell survival by inhibiting apoptosis. However, the mechanism by which HGF inhibits apoptosis is not completely understood. To explore the genes associated with stomach cancer cell survival by HGF, we used cDNA microarray technology and selected 26 genes up- or downregulated in NUGC-3 cells during HGF treatment. Among them, BAD was confirmed to be upregulated at the RNA and protein levels by HGF treatment. We investigated the effect of BAD induced by HGF on cell survival. HGF treatment inhibited apoptosis induced by BAD overexpression and enhanced BAD phosphorylation. Pretreatment of NUGC-3 cells with PI3K inhibitors, LY 294002, decreased HGF-induced BAD phosphorylation on Ser136 whereas an MEK inhibitor, PD 98059, decreased BAD phosphorylation on Ser112. In conclusion, increases in BAD levels as well as BAD phosphoryation by HGF might contribute to HGF-mediated cell survival in NUGC-3 cells.

摘要

肝细胞生长因子（HGF）是一种存活因子，具有通过抑制细胞凋亡来促进细胞存活的强大能力。然而，HGF抑制细胞凋亡的机制尚未完全明确。为了探究与HGF介导的胃癌细胞存活相关的基因，我们使用了cDNA微阵列技术，并筛选出26个在HGF处理期间NUGC-3细胞中表达上调或下调的基因。其中，BAD被证实经HGF处理后在RNA和蛋白质水平均上调。我们研究了HGF诱导的BAD对细胞存活的影响。HGF处理可抑制由BAD过表达诱导的细胞凋亡，并增强BAD的磷酸化。用PI3K抑制剂LY 294002预处理NUGC-3细胞，可降低HGF诱导的Ser136位点的BAD磷酸化，而MEK抑制剂PD 98059则可降低Ser112位点的BAD磷酸化。总之，HGF导致的BAD水平升高以及BAD磷酸化可能有助于NUGC-3细胞中HGF介导的细胞存活。