RRC ID 1954
著者 Ohta M, Tateishi K, Kanai F, Watabe H, Kondo S, Guleng B, Tanaka Y, Asaoka Y, Jazag A, Imamura J, Ijichi H, Ikenoue T, Sata M, Miyagishi M, Taira K, Tada M, Kawabe T, Omata M.
タイトル p53-Independent negative regulation of p21/cyclin-dependent kinase-interacting protein 1 by the sonic hedgehog-glioma-associated oncogene 1 pathway in gastric carcinoma cells.
ジャーナル Cancer Res
Abstract The activation of Hedgehog (Hh) signaling has been implicated in the growth of various tumor types, including gastric carcinoma. However, the precise mechanisms of Hh activation and suppression of tumor growth by the blockade of Hh signaling in gastric carcinoma cells remain unknown. The aim of this study was to elucidate the mechanism of abnormal Hh signaling and the key molecules contributing to dysregulated growth of gastric carcinoma. The Sonic hedgehog (Shh) ligand and its receptor Patched were expressed in all five gastric carcinoma cell lines examined (MKN1, MKN7, MKN45, MKN74, and AGS cells). The blockade of Hh signaling with anti-Shh antibody inhibited the growth of all five gastric carcinoma cell lines. Shh was overexpressed (mean, 12.8-fold) in 8 of 14 (57.0%) cancerous tissue samples from patients with gastric carcinoma as compared with expression in the surrounding noncancerous tissues. The disruption of glioma-associated oncogene 1 (Gli1) by small interfering RNA induced an increase in p21/cyclin-dependent kinase-interacting protein 1 (CIP1), interfered with the G1-S transition, and suppressed cell proliferation. The stimulation or inhibition of Hh signaling did not affect p53 activity and the induction of p21/CIP1 expression and the G1 arrest by inhibition of Hh signaling were not affected by the p53 status. These findings suggest that the overexpression of Shh contributes to constitutive Hh activation and that this signaling pathway negatively regulates p21/CIP1 through a Gli1-dependent and p53-independent mechanism in gastric carcinoma cells.
巻・号 65(23)
ページ 10822-9
公開日 2005-12-1
DOI 10.1158/0008-5472.CAN-05-0777
PII 65/23/10822
PMID 16322228
MeSH Adult Aged Aged, 80 and over Cell Cycle / physiology Cell Line, Tumor Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis* Cyclin-Dependent Kinase Inhibitor p21 / genetics Female Hedgehog Proteins Humans Male Middle Aged RNA Interference RNA, Messenger / biosynthesis RNA, Messenger / genetics RNA, Small Interfering / genetics Signal Transduction Stomach Neoplasms / genetics Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology* Trans-Activators / antagonists & inhibitors Trans-Activators / biosynthesis Trans-Activators / genetics Trans-Activators / physiology* Transcription Factors / antagonists & inhibitors Transcription Factors / biosynthesis Transcription Factors / genetics Transcription Factors / physiology* Transfection Tumor Suppressor Protein p53 / physiology* Up-Regulation Zinc Finger Protein GLI1
IF 9.727
引用数 71
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 MKN45(RCB1001) MKN74(RCB1002) MKN7(RCB0999)