p53 functions as a cell cycle control protein in osteosarcomas.

Abstract

Mutations in the p53 gene have been associated with a wide range of human tumors, including osteosarcomas. Although it has been shown that wild-type p53 can block the ability of E1a and ras to cotransform primary rodent cells, it is poorly understood why inactivation of the p53 gene is important for tumor formation. We show that overexpression of the gene encoding wild-type p53 blocks the growth of osteosarcoma cells. The growth arrest was determined to be due to an inability of the transfected cells to progress into S phase. This suggests that the role of the p53 gene as an antioncogene may be in controlling the cell cycle in a fashion analogous to the check-point control genes in Saccharomyces cerevisiae.

Twenty years of p53 research: structural and functional aspects of the p53 protein

“…The overexpression of p53 protein that is observed in irradiated cells can also be produced by ectopic p53 expression after p53 gene transfer into non irradiated control cells. Non irradiated cells expressing thereby high levels of wildtype p53 have been shown to undergo either cell cycle arrest in G1 (Diller et al, 1990;Lin et al, 1992) or apoptosis (Yonish-Rouach et al, 1991, 1994Shaw et al, 1992).…”

p21WAF1/CIP1 response to genotoxic agents in wild-type TP53 expressing breast primary tumours

“…Wild-type p53 exhibits both growth and transformation suppression activities, giving rise to a G 1 block in cell cycle progression (Diller et al, 1990;Lin et al, 1992), and in some cell types leading to apoptosis (Yonish-Rouach et al, 1991). Deletion of the TP53 gene in transgenic mice results in a massive increase tumour incidence (Donehower et al, 1992), supporting a role for p53 as a tumour suppressor.…”

Cloning of rat GADD45 gene and induction analysis following ionizing radiation in vivo

“…The expression of GADD45 is regulated by p53, such that over-expression of p53 in cultured cells causes G1 arrest and prevents cells from entering the S phase [9][10][11][12]. The null mutant of p53 is unable to arrest cells at G1 after ),-irradiation, but upon transfecting the wild type p53, the G1 arrest is resumed [13].…”