Glycoprotein hormone α-subunit promotes cell proliferation and tumorigenesis in breast cancer

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 in vitro, and in vivo 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. In vitro and in vivo 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.