Close correlation between the dephosphorylation of p53 and growth suppression by transforming growth factor-beta 1 in nasopharyngeal carcinoma cells transduced with adenovirus early region genes.
The mechanism of growth inhibition by transforming growth factor (TGF)-beta 1 was investigated. We examined the growth inhibitory effects of TGF-beta 1 on human nasopharyngeal carcinoma (KB) cells which constitutively expressed p53. TGF-beta 1 suppressed the DNA synthesis of KB cells in a dose-dependent manner. It had minimal effect on adenovirus-2-transduced KB cells expressing either adenovirus early region 1B (E1B) or 1A (E1A) product, which respectively binds to p53 or Rb product and inhibits its function, and no growth inhibition at all was observed with KB cells expressing both E1B and E1A products. Dephosphorylation of the p53 was promoted by TGF-beta 1 stimulation in KB cells, but not in E1B-producing KB cells, which sequestrate the function of p53. The growth inhibition of KB cells by TGF-beta 1 was significantly reduced by treatment with okadaic acid. These results suggest that p53 transduces the antiproliferative signal of TGF-beta 1 possibly through its dephosphorylation.
Mogi
Y
Y
Department of Internal Medicine, Sapporo Medical University School of Medicine.
Kato
J
J
Horimoto
M
M
Takimoto
R
R
Murakami
T
T
Hirayama
A
A
Kohgo
Y
Y
Watanabe
N
N
Niitsu
Y
Y
D017500:Adenovirus E1A Proteins / Q000378:metabolism; D017501:Adenovirus E1B Proteins / Q000378:metabolism; D015153:Blotting, Western; D002455:Cell Division; D004279:DNA, Viral; D004305:Dose-Response Relationship, Drug; D004988:Ethers, Cyclic / Q000494:pharmacology; D016158:Genes, p53; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D019319:Okadaic Acid; D010766:Phosphorylation; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D004279:DNA, Viral; D004988:Ethers, Cyclic; D016212:Transforming Growth Factor beta; D019319:Okadaic Acid