ECRG1, a novel candidate of tumor suppressor gene in the esophageal carcinoma, triggers a senescent program in NIH3T3 cells.
Esophageal cancer-related gene 1 (ECRG1) is a novel tumor-suppressor gene candidate identified from the human esophagus. Previous studies showed that ECRG1 overexpression could inhibit cell growth and induce G1 cell cycle arrest and p15(INK4b) expression by interacting with Miz-1 (Myc-interacting zinc finger protein). Such evidence suggests the alterations in ECRG1 may play an important role in tumorigenesis. To further study the biological function of the ECRG1 gene, we transfected ECRG1 into NIH3T3 cells. Expression of ECRG1 in these cells caused senescence-like changes characterized in terms of altered cell morphology, cell cycle arrest at the G1/S phase, and significantly impaired cell proliferation (P < 0.01). Moreover, NIH3T3 cells transfected with ECRG1 stained positive for SA-beta-gal staining (pH 6.0), which is a specific marker of cellular senescence. We also studied changes in telomerase activity and the related senescence genes, such as p21 and p16. The results indicated that when ECRG1 induced a senescence-like state, telomerase activity was markedly decreased (P < 0.05), and expression of p21 was distinctly increased, whereas no changes were detected in p16 and telomerase-component RNA levels. These findings suggest that ECRG1 may be of importance in murine cell senescence, promoting senescence by regulating expression of p21.
Zhao
Nianxi
N
Department of Etiology and Carcinogenesis, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, People's Republic of China.
Huang
Ge
G
Guo
Liping
L
Lu
Shih-Hsin
SH
D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D016193:G1 Phase / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D012313:RNA / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D057057:Serine Proteases; D019098:Telomerase / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000378:metabolism
D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C446704:TMPRSS11A protein, human; D012313:RNA; D019098:Telomerase; D001616:beta-Galactosidase; D057057:Serine Proteases