The cellular mechanism by which the human endogenous retrovirus ERV-3 env gene affects proliferation and differentiation in a human placental trophoblast model, BeWo.
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.
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Department of Microbiology and Immunology, Wright State University School of Medicine, Dayton, Ohio, 45435, USA.
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D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002822:Choriocarcinoma / Q000235:genetics / Q000473:pathology / Q000821:virology; D006063:Chorionic Gonadotropin / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D019926:Cyclin B / Q000378:metabolism; D020077:Endogenous Retroviruses / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D015752:Genes, env; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D011247:Pregnancy; D013449:Sulfonamides; D014162:Transfection; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism / Q000821:virology*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D006063:Chorionic Gonadotropin; D019926:Cyclin B; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D013449:Sulfonamides; D017868:Cyclic AMP-Dependent Protein Kinases; D020741:rho GTP-Binding Proteins; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide