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ORIGINAL RESEARCH ARTICLE

ECRG1, a Novel Candidate of Tumor Suppressor Gene in the Esophageal Carcinoma, Triggers a Senescent Program in NIH3T3 Cells

Nianxi Zhao^*,, Ge Huang^*, Liping Guo^* and Shih-Hsin Lu^*,1

^* Department of Etiology and Carcinogenesis, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, People’s Republic of China; and School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4660

To whom requests for reprints should be addressed at ¹ Department of Etiology and Carcinogenesis, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, People’s Republic of China. E-mail: shlu{at}public.bta.net.cn

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-ß-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.

Key Words: ECRG1 • esophageal • carcinoma • G1 cell cycle arrest • senescence • telomerase