In cloned osteoblast-like cells, MC3T3-E1, 12-O-tetradeeanoylphorbol-13-acetate (TPA), a protein kinase C activating phorbol ester, and I-oleoyl-2-acetylglycerol (OAG), a specific activator for protein kinase C, stimulated DNA synthesis in a dose-dependent manner. Both TPA and OAG acted synergistically with insulin-like growth factor I to stimulate DNA synthesis. TPA as well as OAG suppressed the increase in alkaline phosphatase activity of MC3T3-E 1 cells induced by parathyroid hormone. These results suggest that protein kinase C is involved in the process which directs osteoblastlike cells toward proliferation.Protein kinase C; Osteoblast
BackgroundPeroxisome proliferator-activated receptor α (PPARα) regulates lipid metabolism in the liver. It is unclear, however, how this receptor changes in liver cancer tissue. On the other hand, mouse carcinogenicity studies showed that PPARα is necessary for the development of liver cancer induced by peroxisome proliferators, and the relationship between PPARα and the development of liver cancer have been the focus of considerable attention. There have been no reports, however, demonstrating that PPARα is involved in the development of human liver cancer.MethodsThe subjects were 10 patients who underwent hepatectomy for hepatocellular carcinoma. We assessed the expression of PPARα mRNA in human hepatocellular carcinoma tissue and non-cancerous tissue, as well as the expression of target genes of PPARα, carnitine palmitoyltransferase 1A and cyclin D1 mRNAs. We also evaluated glyceraldehyde 3-phosphate dehydrogenase, a key enzyme in the glycolytic system.ResultsThe amounts of PPARα, carnitine palmitoyltransferase 1A and glyceraldehyde 3-phosphate dehydrogenase mRNA in cancerous sections were significantly increased compared to those in non-cancerous sections. The level of cyclin D1 mRNA tends to be higher in cancerous than non-cancerous sections. Although there was a significant correlation between the levels of PPARα mRNA and cyclin D1 mRNA in both sections, however the correlation was higher in cancerous sections.ConclusionThe present investigation indicated increased expression of PPARα mRNA and mRNAs for PPARα target genes in human hepatocellular carcinoma. These results might be associated with its carcinogenesis and characteristic features of energy production.
The effect of insulin-like growth factor-I (IGF-I) on calcification in cloned osteoblastlike MC3T3-E1 cells was studied by measuring accumulation of 45Ca into sodium dodecyl sulfate-insoluble, EDTA-extractable structure that appeared after 2 weeks of culture. The accumulation of 45Ca was markedly enhanced by incubating cells with IGF-I after 6 weeks of culture. The enhancement was dose-dependent in a range between 0.1 nM and 100 nM. IGF-I stimulated alkaline phosphatase activity in the cells cultured for 7 weeks dosedependently between 0.1 nM and 100 nM. DNA synthesis examined in the cells cultured for 7 weeks was not influenced by 100 nM IGF-I. These results suggest that IGF-I stimulates Ca-accumulation in osteoblast-like cells without stimulating their proliferation.Calcium, Osteoblast.
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