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Expression of p21 Is Not Required for Senescence of Human Fibroblasts¹

Center for Gerontological Research, Medical College of Pennsylvania and Hahnemann University, Philadelphia, Pennsylvania 19129 [A. S. C. M., V. J. C.] and Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 [A. J. P. K-S.]

Senescence and immortalization have been studied in skin fibroblasts derived from two individuals with the Li-Fraumeni syndrome. These cells inherit one wild-type and one mutant p53 allele and lose the former during culture. Despite this loss, cultures of Li-Fraumeni syndrome cells progressed normally from early passage to replicative senescence. Senescent cells also expressed barely detectable levels of p21 mRNA, and, in marked contrast to normal cultured cells, levels of p21 expression decreased during in vitro aging. Further maintenance for up to 10 months of post-mitotic cultures has led to the isolation of cells with an extended lifespan. Four potentially immortal cultures have continued to proliferate, and two have completed more than 110 population doublings. These results indicate that p53 and p21 are not required for replicative senescence in human fibroblasts. However, their inactivation may enhance the probability of spontaneous immortalization.

¹ This work was supported by NIH Grants AG00131, AG00378, AG00532, and CA53713.

² To whom requests for reprints should be addressed, at Center for Gerontological Research, Allegheny University of the Health Sciences, 2900 Queen Lane, Philadelphia, PA 19129. Phone: (215) 991-8460; Fax: (215) 843-1192.

Received 7/ 6/96. Accepted 8/27/96.

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