Effect of phorbol 12-myristate-13-acetate on cell adhesion in SMMC-7721 human hepatocellular carcinoma cell line and its mechanism.
The gene expression of integrin a5 beta 1 and the ability of cell adhesion of SMMC-7721 hepatocellular carcinoma cell are reported to be altered in the presence of 100nM phorbol 12-myristate-13-acetate (PMA). The ability of cell adhesion to extracellular matrix-fibronectin (Fn) was 18.8%, 38.7% and 56.6% enhancement for 30.60 and 120 mins treatment with 100nM PMA, respectively, as compared with the PMA control. But after 6 and 12 hours, it decreased to 57.4% and 61.1%, whereas the adhesion to polylysine remained the same. Using sufficient amount of anti-a5 and anti-beta 1 mAb to pre-block the adhesion sites we found that cell adhesion to Fn was inhibited by approximately 40%. It seems that other integrins mediate cell adhesion to Fn besides alpha 5 beta 1. The results obtained from the Northern blot with alpha 5 cDNA probe showed that PMA could downregulate the transcription of integrin alpha 5 beta 1 gene from 10 mins to 12 hours. The transcription was lowered to 16.9% of the control after 30 mins. The inhibition rate was still 43.6% after 12-hour treatment. The possible mechanism by which PMA influences the cell adhesion and integrin gene expression is discussed here.
Fu
J Z
JZ
Dept. of Biochemistry, Shanghai Medical University, China.
Zha
X L
XL
D015152:Blotting, Northern; D002273:Carcinogens / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002273:Carcinogens; D005353:Fibronectins; D016023:Integrins; D013755:Tetradecanoylphorbol Acetate