title: 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 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.
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Wenshan
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Weilong
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D055785:Gene Knockdown Techniques; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D024243:HMGB1 Protein; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D004958:Estradiol