Lu Z.,Fudan University |
Lu Z.,Shanghai Key Laboratory of Female Reproductive EndocrineRelated Diseases |
Zhang Y.,Fudan University |
Zhang Y.,Shanghai Key Laboratory of Female Reproductive EndocrineRelated Diseases |
And 17 more authors.
Molecular Medicine Reports | Year: 2014
Previous studies by our group revealed that the phosphoinositide 3kinase (PI3K)/AKT pathway was involved in estrogeninduced metastasis in ovarian cancer cells. In the present study, the role and mechanism of estrogeninduced invasion was further explored using a stable short hairpin RNA (shRNA) estrogen receptor α/β (ER α/β) SKOV3 cell line when ER α and ER β were knocked down by lentiviral infection. The effects of estrogen and LY294002, a PI3K inhibitor, on the invasion of shRNA ER α/β SKOV3 cells were evaluated in vitro and in vivo. 17β estradiol promoted cell invasion, activated phosphorylated AKT in a doseand timedependent manner, decreased Ecadherin and increased cytoplasmic αactinin4 expression. When the PI3K/AKT pathway was suppressed by LY294002, the effect of estrogen was attenuated. Estrogen stimulated the growth of shRNA ER α/β SKOV3 xenograft tumors in nude mice, whereas LY294002 inhibited the growth and antagonized the effect of estrogen. The results indicate that estrogen promotes the invasion of ovarian cancer cells via activation of the PI3K/AKT pathway, downregulation of Ecadherin and upregulation of αactinin4 in an ERindependent manner. Inhibiting the PI3K/AKT pathway may be a useful treatment for ovarian carcinoma.