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KMID : 0939920160480020715
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대한암학회지
2016 Volume.48 No. 2 p.715 ~ p.726
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Caveolin-1 Modulates Docetaxel-Induced Cell Death in Breast Cancer Cell Subtypes through Different Mechanisms
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Kang Jin-Ho
Park Joo-Hee
Lee Hye-Jin
Jo Uk-Hyun
Park Jong-Kuk
Seo Jae-Hong
Kim Yeul-Hong
Kim In-Sun
Park Kyong-Hwa
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Abstract
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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.
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KEYWORD
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Caveolin-1, Breast neoplasm, Apoptosis, Docetaxel
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