Caveolin-1 Modulates Docetaxel-Induced Cell Death in Breast Cancer Cell Subtypes through Different Mechanisms.
- Author:
Jinho KANG
1
;
Joo Hee PARK
;
Hye Jin LEE
;
Ukhyun JO
;
Jong Kuk PARK
;
Jae Hong SEO
;
Yeul Hong KIM
;
Insun KIM
;
Kyong Hwa PARK
Author Information
- Publication Type:In Vitro ; Original Article
- Keywords: Caveolin-1; Breast neoplasm; Apoptosis; Docetaxel
- MeSH: Apoptosis; Breast Neoplasms*; Breast*; Caveolin 1*; Cell Cycle Checkpoints; Cell Death*; Cell Line; Cell Proliferation; Estrogens; Heterografts; MCF-7 Cells; Negotiating; Triple Negative Breast Neoplasms
- From:Cancer Research and Treatment 2016;48(2):715-726
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: Caveolin-1 (CAV-1) expression is more associated with basal-like cancers than estrogen receptor- or ErbB-2-expressing breast cancers. However, the biological relevance of different levels of CAV-1 expression according to subtype in the epithelial compartment of breast cancer remains unclear. MATERIALS AND METHODS: We investigated whether CAV-1 functions as a tumor suppressor and/or modulator of the cytotoxic activity of docetaxel (DTX) in subtypes of breast cancer using in vitro and xenograft models. RESULTS: The levels of CAV-1 expression were closely associated with DTX sensitivity in triple-negative breast cancer cells. In addition, CAV-1 significantly inhibited cell proliferation and modulated DTX-induced apoptosis through cell cycle arrest in the G2/M phase. The mechanisms underlying DTX-induced apoptosis differed in breast cancers according to the levels of CAV-1 expression. DTX robustly enhanced Bcl-2 inactivation by CAV-1 in MDA-MB-231 cells, while p53-mediated cell cycle arrest by DTX was more pronounced in CAV-1-low but p53-functional MCF-7 cells. In parallel with the data from breast cancer cell lines, CAV-1-transfected MCF-7 cells showed higher efficacy of DTX treatment in a xenograft model. CONCLUSION: We clearly demonstrated cooperative effects between CAV-1 and DTX in mediating apoptosis, suggesting that the levels of CAV-1 expression might be an important indicator for DTX use in breast cancer.
