Caveolin-1 Modulates Docetaxel-Induced Cell Death in Breast Cancer Cell Subtypes through Different Mechanisms.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Jinho
J
Kang
Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Joo Hee
JH
Park
Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Hye Jin
HJ
Lee
Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Ukhyun
U
Jo
Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea.
Jong Kuk
JK
Park
Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Jae Hong
JH
Seo
Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Yeul Hong
YH
Kim
Department of Pathology, Korea University College of Medicine, Seoul, Korea.
Insun
I
Kim
Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Kyong Hwa
KH
Park
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051242:Caveolin 1 / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D000077143:Docetaxel; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D011960:Receptors, Estrogen / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*; D064726:Triple Negative Breast Neoplasms / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D051242:Caveolin 1; D011960:Receptors, Estrogen; C495901:TP53 protein, human; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; D000077143:Docetaxel
Apoptosis; Breast neoplasm; Caveolin-1; Docetaxel