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促性腺激素受体表达降低与更具侵袭性的卵巢癌表型相关。

Reduced Gonadotrophin Receptor Expression Is Associated with a More Aggressive Ovarian Cancer Phenotype.

机构信息

Adelaide Medical School, Robinson Research Institute, University of Adelaide, Adelaide, SA 5000, Australia.

School of Biological Science, Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia.

出版信息

Int J Mol Sci. 2020 Dec 23;22(1):71. doi: 10.3390/ijms22010071.

Abstract

Follicle-stimulating hormone (FSH) and luteinising hormone (LH) play important roles in regulating cell growth and proliferation in the ovary. However, few studies have explored the expression of FSH and LH receptors (FSHR and LHCGR) in ovarian cancer, and their functional roles in cancer progression remain inconclusive. This study investigated the potential impact of both mRNA (, ) and protein (FSHR, LHCGR) expression on ovarian cancer progression using publicly available online databases, qRT-PCR (high grade serous ovarian cancers, HGSOC, = 29 and benign ovarian tumors, = 17) and immunohistochemistry (HGSOC, = 144). In addition, we investigated the effect of and siRNA knockdown on the pro-metastatic behavior of serous ovarian cancer cells in vitro. High or high expression in patients with all subtypes of high-grade ovarian cancer was significantly associated with longer progression-free survival (PFS) and overall survival (OS). High FSHR protein expression was associated with increased PFS ( = 0.050) and OS ( = 0.025). HGSOC patients with both high FSHR and high LHCGR protein levels had the best survival outcome, whilst both low FSHR and low LHCGR expression was associated with poorest survival ( = 0.019). Knockdown of FSHR significantly increased the invasion of serous ovarian cancer cells (OVCAR3 and COV362) in vitro. LHCGR knockdown also promoted invasion of COV362 cells. This study highlights that lower FSHR and LHCGR expression is associated with a more aggressive epithelial ovarian cancer phenotype and promotes pro-metastatic behaviour.

摘要

卵泡刺激素 (FSH) 和黄体生成素 (LH) 在调节卵巢细胞生长和增殖方面发挥着重要作用。然而,很少有研究探讨 FSH 和 LH 受体 (FSHR 和 LHCGR) 在卵巢癌中的表达及其在癌症进展中的功能作用。本研究使用公共可用的在线数据库、qRT-PCR(高级别浆液性卵巢癌,HGSOC,=29 和良性卵巢肿瘤,=17)和免疫组织化学(HGSOC,=144)来研究两种 mRNA(,)和蛋白(FSHR,LHCGR)表达对卵巢癌进展的潜在影响。此外,我们还研究了 和 siRNA 敲低对浆液性卵巢癌细胞体外促转移行为的影响。所有高级别卵巢癌亚型患者的 或 高表达与更长的无进展生存期 (PFS) 和总生存期 (OS) 显著相关。高 FSHR 蛋白表达与 PFS 增加相关(=0.050)和 OS(=0.025)。具有高 FSHR 和高 LHCGR 蛋白水平的 HGSOC 患者具有最佳的生存结局,而低 FSHR 和低 LHCGR 表达与最差的生存相关(=0.019)。FSHR 的敲低显著增加了浆液性卵巢癌细胞(OVCAR3 和 COV362)的体外侵袭。LHCGR 敲低也促进了 COV362 细胞的侵袭。本研究强调,较低的 FSHR 和 LHCGR 表达与更具侵袭性的上皮性卵巢癌表型相关,并促进促转移行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1ee/7793521/38f447cdd849/ijms-22-00071-g001.jpg

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