h-89 and Uterine-Neoplasms

The env region of the human endogenous retrovirus ERV-3 is expressed during differentiation of trophoblast and the choriocarcinoma BeWo. Stable transfectants with ERV-3 env exhibit most aspects of trophoblast differentiation, including inhibition of cell proliferation, changes in cell morphology, and increased production of beta-hCG mRNA. In this study, the cellular mechanism of induction of BeWo cell differentiation by ERV-3 env was investigated. In BeWo cells stably transfected with ERV-3 env, the production of beta-hCG mRNA and hCG protein was increased. Intracellular cAMP level was markedly increased over that of vector transfected cells. The effect on beta-hCG protein production was inhibited by H89, a protein kinase A (PKA) inhibitor, while protein kinase C (PKC) and protein tyrosine kinase (PTK) inhibitors had no effect. The expression of a major cell cycle promoter, cyclin B, was markedly reduced while expression of p21, a negative regulator of the cell cycle, was up-regulated. Inhibition of ERV-3 env induced hCG production with H89 had no significant effect on cell growth when compared with cells transfected with vector alone.

Topics: Cell Differentiation; Cell Division; Choriocarcinoma; Chorionic Gonadotropin; Cyclic AMP-Dependent Protein Kinases; Cyclin B; Endogenous Retroviruses; Enzyme Inhibitors; Female; Gene Expression; Genes, env; Humans; Isoquinolines; Pregnancy; rho GTP-Binding Proteins; Sulfonamides; Transfection; Trophoblasts; Tumor Cells, Cultured; Uterine Neoplasms