Abstrakt: |
The envregion of the human endogenous retrovirus ERV-3 is expressed during differentiation of trophoblast and the choriocarcinoma BeWo. Stable transfectants with ERV-3 envexhibit most aspects of trophoblast differentiation, including inhibition of cell proliferation, changes in cell morphology, and increased production of β-hCG mRNA. In this study, the cellular mechanism of induction of BeWo cell differentiation by ERV-3 envwas investigated. In BeWo cells stably transfected with ERV-3 env, the production of β-hCG mRNA and hCG protein was increased. Intracellular cAMP level was markedly increased over that of vector transfected cells. The effect on β-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 envinduced hCG production with H89 had no significant effect on cell growth when compared with cells transfected with vector alone. |