Department of Biochemistry and Pharmacy , Abo Akademi University , Turku , Finland .
Cell Growth Differ 6 : 457-64 ( 1995)
Abstract
Treatment of the U-2 OS human osteosarcoma cell line with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate ( TPA ) dramatically decreased the rate of DNA synthesis .
This decrease in proliferation as well as the change in morphology of the TPA-treated cells can be blocked by the protein kinase C inhibitor GF 109203X .
The U-2 OS cells are known to express the c-sis oncogene [ platelet-derived growth factor ( PDGF ) B-chain ] , PDGF-A , and receptors for PDGF , thus providing a potential autocrine loop of growth stimulation .
TPA was found to induce the expression of both the PDGF-A and the PDGF-B chains .
However , the levels of the PDGF receptor beta subunits and of the PDGF-BB inducable tyrosine phosphorylation of the PDGF receptor were markedly reduced .
The TPA treatment of the U-2 OS cells also induced changes typical for maturing bone cells , such as increased expression levels of alkaline phosphatase and osteopontin .
The expression levels of type I collagen and bone sialoprotein were reduced .
The results show a TPA-dependent down-regulation of the PDGF receptor beta subunits that correlates with an increased expression of osteoblast phenotypic markers .