Caveolin-1 modulates docetaxel-induced cell death in breast cancer cell subtypes through different mechanisms

Jinho Kang, Joo Hee Park, Hye Jin Lee, Ukhyun Jo, Jong Kuk Park, Jae Hong Seo, Yeul Hong Kim, Insun Kim, Kyong Hwa Park

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)715-726
Number of pages12
JournalCancer Research and Treatment
Volume48
Issue number2
DOIs
Publication statusPublished - 2016 Apr 1

Keywords

  • Apoptosis
  • Breast neoplasms
  • Caveolin 1
  • Docetaxel

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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