Phenotypic modification of human osteosarcoma cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate.
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.
Ringbom-Anderson
T
T
Department of Biochemistry and Pharmacy, Abo Akademi University, Turku, Finland.
Sandberg
M
M
Andersson
G
G
Akerman
K E
KE
D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D006801:Humans; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D010703:Phorbol Esters / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis*; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D010703:Phorbol Esters; D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor