Lin L, Xu B, Rote N S
Department of Microbiology and Immunology, Wright State University School of Medicine, Dayton, Ohio, 45435, USA.
Placenta. 2000 Jan;21(1):73-8. doi: 10.1053/plac.1999.0443.
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.
人类内源性逆转录病毒ERV - 3的env区域在滋养层细胞和绒癌BeWo细胞分化过程中表达。携带ERV - 3 env的稳定转染细胞表现出滋养层细胞分化的大多数特征，包括细胞增殖受抑制、细胞形态改变以及β - hCG mRNA产量增加。在本研究中，对ERV - 3 env诱导BeWo细胞分化的细胞机制进行了研究。在稳定转染了ERV - 3 env的BeWo细胞中，β - hCG mRNA和hCG蛋白的产量增加。细胞内cAMP水平比转染载体的细胞显著升高。蛋白激酶A（PKA）抑制剂H89可抑制对β - hCG蛋白产生的影响，而蛋白激酶C（PKC）和蛋白酪氨酸激酶（PTK）抑制剂则无作用。细胞周期主要启动子细胞周期蛋白B的表达显著降低，而细胞周期负调控因子p21的表达上调。与单独转染载体的细胞相比，用H89抑制ERV - 3 env诱导的hCG产生对细胞生长无显著影响。
