Caveolin-1 functions as a key regulator of 17β-estradiol-mediated autophagy and apoptosis in BT474 breast cancer cells.

Abstract

Estradiol (E2) acts as a crucial regulator of cell growth by mediating autophagy and apoptosis in breast cancer cells. Caveolin-1 plays a key role in carcinogenesis through its diverse roles in membrane trafficking, cholesterol transport and cellular signal transduction. However, it remains unknown as to how caveolin-1 is associated with E2-mediated autophagy and apoptosis in breast cancer cells. To resolve this issue, in the present study, we used the human breast cancer cell line, BT474, in which caveolin-1 is abundantly expressed. We demonstrated that treatment with E2 increased the expression of caveolin-1, high mobility group box1 protein (HMGB1) and autophagy-related proteins [Beclin-1, light chain (LC3)-II and Atg12/5] in a time-dependent manner and inhibited the apoptosis of BT474 cells. Following the knockdown of caveolin-1 expression using small interfering RNA (siRNA), the expression of HMGB1, LC3-II and Atg12/5 was decreased, autophgosome formation was inhibited and apoptosis was induced; however, Beclin-1 expression was not affected. Furthermore, we knocked down HMGB1 to validate the role of HMGB1 in E2/caveolin‑1-regulated autophagy and apoptosis. Notably, the knockdown of HMGB1 decreased the expression of Beclin-1 and LC3-II and attenuated autophgosome formation and promoted apoptosis. Furthmore, caveolin-1 or HMGB1 knockdown markedly suppressed E2-induced cell growth. These results suggest that caveolin-1 is a positive regulator for E2-induced cell growth by promoting auptophagy and inhibiting apoptosis in BT474 cells.