Zhou Jun, Zhu Xuan, Wu Shijie, Chen Huihui, Chen Yiding
Department of Breast Surgery, The Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
Department of Radiation Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
Oncol Lett. 2022 May;23(5):142. doi: 10.3892/ol.2022.13263. Epub 2022 Mar 11.
The glycoprotein hormone α-subunit (CGA) is implicated in the occurrence and progression of a number of solid tumors. However, its role in breast cancer remains unclear. The present study aimed to investigate the biological functions and mechanisms of action of CGA in breast cancer. CGA protein expression was evaluated in clinical breast cancer specimens using immunohistochemistry. The association between CGA expression and patient prognosis was determined using the Kaplan-Meier method and Mantel-Cox test. At the same time, CGA mRNA and protein expression was explored in a normal mammary epithelial cell line and breast cancer cell lines. Breast cancer cell lines overexpressing or deficient in CGA were established, and the effect of CGA on cell proliferation was evaluated , and using a mouse xenograft tumor model. Intracellular signaling pathway activities were evaluated using western blotting in CGA-overexpressing or -depleted cells. Increased CGA protein expression was significantly associated with a poor prognosis in patients with breast cancer. Furthermore, while CGA mRNA and protein expression level was negligible in normal mammary epithelial cells, it was elevated in breast cancer cell lines. and experiments showed that CGA overexpression enhanced breast cancer cell proliferation via activation of the epidermal growth factor receptor, extracellular signal-regulated kinase 1/2 and serine/threonine kinase Akt signaling cascades. The present results suggest that CGA is upregulated in breast cancer tissues and that it is associated with a poor prognosis. CGA may serve as a candidate for developing targeted therapies for breast cancer.
糖蛋白激素α亚基(CGA)与多种实体瘤的发生和进展有关。然而,其在乳腺癌中的作用仍不清楚。本研究旨在探讨CGA在乳腺癌中的生物学功能及作用机制。采用免疫组织化学方法评估临床乳腺癌标本中CGA蛋白的表达。使用Kaplan-Meier法和Mantel-Cox检验确定CGA表达与患者预后之间的关联。同时,在正常乳腺上皮细胞系和乳腺癌细胞系中探索CGA mRNA和蛋白的表达。建立了CGA过表达或缺失的乳腺癌细胞系,使用小鼠异种移植瘤模型评估CGA对细胞增殖的影响,并通过蛋白质印迹法评估CGA过表达或缺失细胞中的细胞内信号通路活性。CGA蛋白表达增加与乳腺癌患者预后不良显著相关。此外,虽然CGA mRNA和蛋白在正常乳腺上皮细胞中的表达水平可忽略不计,但在乳腺癌细胞系中升高。实验表明,CGA过表达通过激活表皮生长因子受体、细胞外信号调节激酶1/2和丝氨酸/苏氨酸激酶Akt信号级联反应增强乳腺癌细胞增殖。目前的结果表明,CGA在乳腺癌组织中上调,且与预后不良相关。CGA可能作为开发乳腺癌靶向治疗的候选分子。