PinX1 Inhibits Telomerase Activity in Gastric Cancer Cells Through Mad1/c-Myc Pathway

被引：24
作者：
Wang, Hong-bin [1 ,2 ]
Wang, Xing-wei [1 ]
Zhou, Gang [1 ]
Wang, Wei-qiang [1 ]
Sun, Yong-gang [1 ]
Yang, Shi-ming [1 ]
Fang, Dian-chun [1 ]
机构：
[1] Third Mil Med Univ, SW Hosp, Dept Gastroenterol, Chongqing 400038, Peoples R China
[2] 324 Hosp PLA, Chongqing, Peoples R China
来源：
JOURNAL OF GASTROINTESTINAL SURGERY | 2010年 / 14卷 / 08期
关键词：
Cell growth; Gastric carcinoma cell; PinX1; gene; Telomerase; Molecular mechanism; REVERSE-TRANSCRIPTASE GENE; CATALYTIC SUBUNIT; HTERT GENE; C-MYC; TUMOR-CELLS; DOWN-REGULATION; IN-VITRO; EXPRESSION; CARCINOMA; PROMOTER;
D O I：
10.1007/s11605-010-1253-4
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
The aim of this study was to investigate the role of Mad1/c-Myc in telomerase regulation in gastric cancer cells in order to gain insight into telomerase activity and to evaluate PinX1 as a putative inhibitor of gastric cancer. PinX1 and PinX1siRNA eukaryotic expression vectors were constructed by recombinant technology and transfected into gastric carcinoma cells using Lipofectamine (TM) 2000. Telomerase activity was measured by the telomeric repeat amplification protocol. Apoptosis of gastric cancer cells was analyzed by flow cytometry and transmission electron microscopy. Reverse transcription-polymerase chain reaction and Western blotting were used to assess the expression levels of PinX1 and Mad1/c-Myc. We found that PinX1-negative gastric cancer cells showed significantly higher telomerase activity than did the PinX1-postive cells. PinX1-transfection reduced telomerase activity in PinX1-negative gastric cancer cells and exhibited an upregulation of Mad1 and downregulation of c-Myc expression. Pinx1 RNAi treatment led to downregulation of Mad1 and upregulation of c-Myc. Suppression of telomerase activity mediated by PinX1 is involved in the Mad1/c-Myc pathway.
引用
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页码：1227 / 1234
页数：8
相关论文
共 36 条
[21]   The correlation of genetic instability of PINX1 gene to clinico-pathological features of gastric cancer in the Chinese population [J].
Ma, Yingyu ;
Wu, Liang ;
Liu, Cuiping ;
Xu, Liqian ;
Li, Dongmei ;
Li, Ji-Cheng .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2009, 135 (03) :431-437
[22]   hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization [J].
Meyerson, M ;
Counter, CM ;
Eaton, EN ;
Ellisen, LW ;
Steiner, P ;
Caddle, SD ;
Ziaugra, L ;
Beijersbergen, RL ;
Davidoff, MJ ;
Liu, QY ;
Bacchetti, S ;
Haber, DA ;
Weinberg, RA .
CELL, 1997, 90 (04) :785-795
[23]   Telomerase catalytic subunit homologs from fission yeast and human [J].
Nakamura, TM ;
Morin, GB ;
Chapman, KB ;
Weinrich, SL ;
Andrews, WH ;
Lingner, J ;
Harley, CB ;
Cech, TR .
SCIENCE, 1997, 277 (5328) :955-959
[24]   Mitotic checkpoint gene MAD1 in hepatocellular carcinoma is associated with tumor recurrence after surgical resection [J].
Nam, Chang Woo ;
Park, Neung Hwa ;
Park, Bo Ryung ;
Shin, Jung Woo ;
Jung, Seok Won ;
Na, Yang Won ;
Seo, Jae Hee .
JOURNAL OF SURGICAL ONCOLOGY, 2008, 97 (07) :567-571
[25]   In vivo and in vitro analyses of Myc for differential promoter activities of the human telomerase (hTERT) gene in normal and tumor cells [J].
Oh, S ;
Song, YH ;
Kim, UJ ;
Yim, J ;
Kim, TK .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 263 (02) :361-365
[26]   Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT) [J].
Poole, JC ;
Andrews, LG ;
Tollefsbol, TO .
GENE, 2001, 269 (1-2) :1-12
[27]   Differential transcriptional regulation of human telomerase in a cellular model representing important genetic alterations in esophageal squamous carcinogenesis [J].
Quante, M ;
Heeg, S ;
von Werder, A ;
Goessel, G ;
Fulda, C ;
Doebele, M ;
Nakagawa, H ;
Beijersbergen, R ;
Blum, HE ;
Opitz, OG .
CARCINOGENESIS, 2005, 26 (11) :1879-1889
[28]   A survey of telomerase activity in human cancer [J].
Shay, JW ;
Bacchetti, S .
EUROPEAN JOURNAL OF CANCER, 1997, 33 (05) :787-791
[29]  
Takakura M, 1999, CANCER RES, V59, P551
[30]   Myc activates telomerase [J].
Wang, J ;
Xie, LY ;
Allan, S ;
Beach, D ;
Hannon, GJ .
GENES & DEVELOPMENT, 1998, 12 (12) :1769-1774
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