p53 gene mutations and p21 protein expression induced independently of p53, by TGF-beta and gamma-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.
Yoneda
K
K
Department of Oral Surgery, Kochi Medical School, Japan.
Yokoyama
T
T
Yamamoto
T
T
Hatabe
T
T
Osaki
T
T
D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics* / Q000528:radiation effects; D005720:Gamma Rays; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016212:Transforming Growth Factor beta