PinX1 inhibits telomerase activity in gastric cancer cells through Mad1/c-Myc pathway.

Abstract

INTRODUCTION:

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.

METHODS:

PinX1 and PinX1siRNA eukaryotic expression vectors were constructed by recombinant technology and transfected into gastric carcinoma cells using Lipofectamine 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.

RESULTS:

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.

CONCLUSION:

Suppression of telomerase activity mediated by PinX1 is involved in the Mad1/c-Myc pathway.

• Authors: Hong-bin Wang, Xing-wei Wang, Gang Zhou, Wei-qiang Wang, Yong-gang Sun, Shi-ming Yang, Dian-chun Fang
• Journal: Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract (J Gastrointest Surg) Vol. 14 Issue 8 Pg. 1227-34 (Aug 2010) ISSN: 1873-4626 [Electronic] United States
• PMID: 20544396 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Cell Cycle Proteins
• DNA-Binding Proteins
• MAD1L1 protein, human
• MYCBP protein, human
• Nuclear Proteins
• PINX1 protein, human
• RNA, Neoplasm
• Transcription Factors
• Tumor Suppressor Proteins
• Telomerase

Topics

• Apoptosis
• Blotting, Western
• Cell Cycle Proteins (genetics, metabolism)
• Cell Line, Tumor
• DNA-Binding Proteins (genetics, metabolism)
• Flow Cytometry
• Gastric Mucosa (metabolism, ultrastructure)
• Gene Expression Regulation, Neoplastic
• Genes, myc
• Humans
• Microscopy, Electron, Transmission
• Nuclear Proteins (genetics, metabolism)
• RNA, Neoplasm (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Stomach Neoplasms (genetics, metabolism, pathology)
• Telomerase (genetics, metabolism)
• Transcription Factors (genetics, metabolism)
• Tumor Suppressor Proteins (genetics, metabolism)