Liu Y, Hou Y, Ma L, Sun C, Pan J, Yang Y, Zhou H, Zhang J
Department of Gynecology, the Second Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, China.
Department of Reproduction and Genetics, the Second Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, China.
Braz J Med Biol Res. 2017 Feb 20;50(3):e6057. doi: 10.1590/1414-431X20166057.
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.
卵巢癌是女性最常见的恶性肿瘤之一。信号素4D（sema 4D）参与多种癌症的进展。在存在雌激素样配体的情况下，雌激素受体（ERα和ERβ）通过转录调控参与乳腺癌和卵巢癌的进展。本研究的目的是探讨sema 4D的作用，并阐明ERα和ERβ对卵巢癌中sema 4D表达的调控模式。卵巢癌SKOV-3细胞中sema 4D水平上调。恶性卵巢癌患者的sema 4D水平显著高于对照组，提示sema 4D在卵巢癌中起癌基因作用。与正常卵巢IOSE80上皮细胞相比，SKOV-3细胞中ERα表达上调。相反，在SKOV-3细胞中观察到ERβ下调。通过在SKOV-3细胞中强制过表达ERα和ERβ来建立ERα+和ERβ+ SKOV-3细胞系。用雌激素受体激动剂17β-雌二醇（E2）孵育ERα+ SKOV-3细胞可显著增强sema 4D表达和细胞增殖率。用E2孵育时，ERβ+ SKOV-3细胞的sema 4D表达和细胞增殖较低。用ICI182-780抑制剂阻断ERα和ERβ活性后，ERα+和ERβ+ SKOV-3细胞的sema 4D表达和细胞增殖恢复到对照水平。综上所述，数据表明sema 4D表达与卵巢癌进展呈正相关。ERα正向调节sema 4D表达并加速细胞增殖。ERβ负向调节sema 4D表达并抑制细胞增殖。
