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

Wang,Rui; He,Wenshan; Li,Zhi; Chang,Weilong; Xin,Yue; Huang,Tao

doi:10.3892/ijmm.2014.1836

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

Authors:
- Rui Wang
- Wenshan He
- Zhi Li
- Weilong Chang
- Yue Xin
- Tao Huang
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Affiliations: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: July 7, 2014 https://doi.org/10.3892/ijmm.2014.1836
Pages: 822-827

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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 box 1 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.

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