Advances in Brief la,25-Dihydroxyvitamin D3 Enhances 12-0-Tetradecanoylphorbol-13-acetate- induced T\imorigenic Transformation and Osteopontin Expression in Mouse JB6 Epidermal Cells1

To study the role of la,25-dihydroxyvitamin I), (calcitrici) in tumor promotion, we used JB6 C141.Sa cells, a mouse epidermal cell model of tumor promotion. The phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) irreversibly induces anchorage-independent growth and (urnorigenicity in these cells. Since we previously showed (hat calcitrici does not transform these cells but inhibits their proliferation, we hypothesized that calcitrici would inhibit TPA-induced transformation. Concurrent treatment of JB6 C141.5a cells with TPA and calcitrici revealed that calcitrici enhanced (1.7to 10-fold, depending on dose) TPA-induced an chorage-independent growth without enhancing cell proliferation. Fur thermore, a more than additive effect on osteopontin mRNA and protein levels was observed with concurrent drug treatment, which yielded a more highly phosphorylated form of osteopontin. These studies suggest coordi nate regulation between the signaling pathways for calcitrici and TPA in JB6 ('141.5a cells and further implicate expression of phosphorylated osteopontin in tumorigenesis.