Hypoxia enhances c-Met/HGF receptor expression and signaling by activating HIF-1α in human salivary gland cancer cells

被引：57

作者：

Hara, Shingo ^{[1
]}

Nakashiro, Koh-ichi ^{[1
]}

Klosek, Sebastian K. ^{[1
]}

Ishikawa, Tohru ^{[1
]}

Shintani, Satoru ^{[1
]}

Hamakawa, Hiroyuki ^{[1
]}

机构：

[1] Ehime Univ, Sch Med, Dept Oral & Maxillofacial Surg, Toon, Ehime 7910295, Japan

来源：

ORAL ONCOLOGY | 2006年 / 42卷 / 06期

关键词：

c-Met; hypoxia; HIF-1; alpha; invasion; salivary gland cancer;

D O I：

10.1016/j.oraloncology.2005.10.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Hypoxia increases the invasive and metastatic potential of tumor cells. Increased expression of c-Met/hepatocyte growth factor (HGF)-receptor protein in response to hypoxia in thyroid papillary carcinomas is hypoxia-inducible factor-1 (HIF-1) dependent. Both HGF and c-Met are expressed in human salivary gland cancers. In the current study, we tested whether c-Met expression was regulated by hypoxia and HIF-1 alpha using two human salivary gland cancer cell lines: GFP-ACC2 and GFP-ACCM. Hypoxia enhanced the expression of HIF-1 alpha in both cell lines, whereas c-Met was markedly induced only in the GFP-ACCM cells, which have metastatic potential. In the latter, hypoxia also promoted HGF-induced invasiveness. Synthetic small-interfering RNA specific for HIF-1 alpha inhibited HIF-1 alpha expression in the GFP-ACCM cells, and also suppressed the increase in c-Met expression and HGF-induced invasiveness under hypoxic conditions. These results suggest that hypoxia activates the HGF/c-Met system via HIF-1 alpha in human salivary gland cancers and might be involved in their metastasis. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：593 / 598

页数：6

共 30 条

[1]

Birchmeier W, 1997, CIBA F SYMP, V212, P230

[2] Oxygen sensing and molecular adaptation to hypoxia [J].