title: Regulation of semaphorin 4D expression and cell proliferation of ovarian cancer by ERalpha and ERbeta.
abstract: Ovarian cancer is one of the most common malignancies in women. Semaphorin 4D (sema 4D) is involved in the progress of multiple cancers. In the presence of estrogen-like ligands, estrogen receptors (ERα and ERβ) participate in the progress of breast and ovarian cancers by transcriptional regulation. The aim of the study was to investigate the role of sema 4D and elucidate the regulatory pattern of ERα and ERβ on sema 4D expression in ovarian cancers. Sema 4D levels were up-regulated in ovarian cancer SKOV-3 cells. Patients with malignant ovarian cancers had significantly higher sema 4D levels than controls, suggesting an oncogene role of sema 4D in ovarian cancer. ERα expressions were up-regulated in SKOV-3 cells compared with normal ovarian IOSE80 epithelial cells. Conversely, down-regulation of ERβ was observed in SKOV-3 cells. Forced over-expression of ERα and ERβ in SKOV-3 cells was manipulated to establish ERα+ and ERβ+ SKOV-3 cell lines. Incubation of ERα+ SKOV-3 cells with ERs agonist 17β-estradiol (E2) significantly enhanced sema 4D expression and rate of cell proliferation. Incubated with E2, ERβ+ SKOV-3 cells showed lower sema 4D expression and cell proliferation. Blocking ERα and ERβ activities with ICI182-780 inhibitor, sema 4D expressions and cell proliferation of ERα+ and ERβ+ SKOV-3 cells were recovered to control levels. Taken together, the data showed that sema 4D expression was positively correlated with the progress of ovarian cancer. ERα positively regulated sema 4D expression and accelerated cell proliferation. ERβ negatively regulated sema 4D expression and inhibited cell multiplication.
authors.affiliation: Department of Gynecology, the Second Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Gynecology, the Second Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Reproduction and Genetics, the Second Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, China.
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Gynecology, the Second Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, China.
authors.forename: C
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Gynecology, the Second Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, China.
authors.forename: J
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Gynecology, the Second Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Gynecology, the Second Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, the Second Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism*; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D039961:Semaphorins