Regulation of C-myc protooncogene expression in osteoblastic cells by arachidonic acid metabolites: relationship to proliferation.

Prostaglandin E2 and leukotriene B4 are metabolites of arachidonic acid with well-characterized effects on osteoblastic cells. Prostaglandin E2 has been shown to be a potent bone-resorbing agent and to stimulate as well as inhibit osteoblastic cell proliferation. Leukotriene B4 has also been demonstrated to stimulate or inhibit osteoblastic cell proliferation, depending on the cell type tested. In the present study, the potential relationship of the effects of prostaglandin E2 and leukotriene B4 on osteoblastic cell proliferation to c-myc protooncogene expression was investigated. Prostaglandin E2 has been shown previously to inhibit normal rat osteoblastic cell proliferation. The present studies show that prostaglandin E2 at 10(-6) M decreased c-myc expression in these cells. In the human osteoblastic osteosarcoma cell line, G292, prostaglandin E2 increased c-myc expression and inhibited proliferation. In contrast, epidermal growth factor increased DNA synthesis as well as c-myc expression. Prostaglandin E2 also inhibited proliferation of another human osteoblastic osteosarcoma cell line, Saos-2, but it did not produce any changes in c-myc expression. In these cells, epidermal growth factor did not affect either DNA synthesis or c-myc expression. Leukotriene B4 did not show any effects on c-myc expression in any of the osteoblastic cells tested.