ISSN:
1432-1335
Keywords:
Key words Tumor necrosis factor α
;
Early-response genes
;
Liver carcinogen
;
mRNA stabilization
;
Protein phosphatase inhibitor
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Nodularin is a new liver carcinogen possessing a potent tumor-promoting activity in rat liver, mediated through inhibition of protein phosphatases 1 and 2A, and a weak initiating activity. Since we previously reported evidence that nodularin up-regulated expression of the tumor necrosis factor α gene (TNFα) and early-response genes in rat liver after its i.p. administration, and since TNFα had tumor-promoting activity in vitro, it is possible that TNFα itself is involved in liver tumor promotion. We investigated whether hepatocytes themselves induce expression of the TNFα gene and early-response genes in primary cultured rat hepatocytes treated with nodularin. Like nodularin, microcystin-LR, which is another liver tumor promoter belonging to the okadaic acid class, strongly induced TNFα gene expression in rat hepatocytes, as well as TNFα release from those cells into the medium. On the other hand, 12-O-tetradecanoylphorbol-13-acetate, which has been reported to induce no tumor promotion in rat liver, induced no apparent expression of the TNFα gene in primary cultured rat hepatocytes. As for the expression of early-response genes, 1 μM nodularin or microcystin-LR induced expression of the c-jun, jun B, jun D, c-fos, fos B and fra-1 genes in the hepatocytes, and the expression of these genes was prolonged up to 24 h, suggesting mRNA stabilization induced by inhibition of protein phosphatases 1 and 2A. This paper presents new evidence that the TNFα gene and early-response genes were expressed in hepatocytes treated with a liver tumor promoter.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01372544
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