p53 gene mutations and p21 protein expression induced independently of p53, by TGF-β and γ-rays in squamous cell carcinoma cells

p53 gene mutation and the influence of TGF-beta and gamma-rays on p21 promoter activity, p21 mRNA and protein expression were investigated in nine cell lines (OSC-1 to -9) established from metastatic squamous cell carcinomas (SCC) of the cervical lymph nodes. The direct DNA sequence analysis of exons 2 to 11 of the p53 gene revealed 16 point mutations in all cell lines, but neither deletions nor additions were observed. TGF-beta upregulated p21 promoter activity by approximately 2-fold of the control and concurrently increased p21 mRNA expression, except in OSC-8 and -9. However, gamma-rays suppressed p21 promoter activity, although p21 mRNA expression in irradiated cells was increased except for OSC-8 and -9. In parallel with the messenger expression, p21 protein expression was strongly increased by TGF-beta, but only weakly increased by gamma-rays. These results indicate that point mutation of the p53 gene is frequent in metastatic SCC cells and p21 mRNA and its protein expression is p53-independently induced by both TGF-beta and gamma-rays, although the mechanism of induction by TGF-beta and gamma-rays is different. (C) 1999 Elsevier Science Ltd. All rights reserved.