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.