REGULAR ARTICLES Cell Research (2002); 12(3-4):229-233

Senescence-like changes induced by expression of p21^Waf1/Cip1 in NIH3T3 cell line

Xi CHEN¹, Wei ZHANG², Yun Fei GAO¹, Xiao Qin SU¹, Zhong He ZHAI^1,*

¹College of Life Sciences, Peking University, Beijing 100871, China
²The Key Laboratory of Cell Proliferation and Regulation Biology of the Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China

ABSTRACT

    P21^Waf1/Cip1 is a potent cyclin-dependent kinase inhibitor. As a downstream mediator of p53, p21^Waf1/Cip1 involves in cell cycle arrest, differentiation and apoptosis. Previous studies in human cells provided evidence for a link between p21^Waf1/Cip1 and cellular senescence. While in murine cells, the role of p21^Waf1/Cip1 is indefinite. We explored this issue using NIH3T3 cells with inducible p21^Waf1/Cip1 expression. Induction of p21^Waf1/Cip1 triggered G1 growth arrest, and NIH3T3-p21 cells exhibited morphologic features, such as enlarged and flattened cellular shape, specific to the senescence phenotype. We also showed that p21^Waf1/Cip1-transduced NIH3T3 cells expressed b -galactosidase activity at pH 6.0, which is known to be a marker of senescence. Our results suggest that p21^Waf1/Cip1 can also induce senescence-like changes in murine cells.

Key words: p21^Waf1/Cip1, senescence, inducible expression, cell cycle arrest.

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