Estrogen-independent effects of ER-α36 in ER-negative breast cancer

Steroids. 2012 May;77(6):666-73. doi: 10.1016/j.steroids.2012.02.013. Epub 2012 Feb 27.

Abstract

Estrogen receptor-alpha 36 (ER-α36) is a variant of ER-α that has been found to be expressed in conventional ER (ER-α66)-negative breast cancer cell lines and human breast cancer samples. In this study, we found that, using immunohistochemical study, ER-α36 expression was significantly higher in ER-negative tumors than in ER-positive tumors although the expression was not associated with other clinicopathological characteristics. We then constructed an ER-α36-specific microRNA hairpin vector and established stable ER-α36 knockdown cells, and found that the knockdown cells were more sensitive to paclitaxel; the c-Jun N-terminal kinase pathway appeared to be involved in the mechanism. Downregulation of ER-α36 also resulted in decreased migration and invasion. These changes were estrogen independent. Our findings indicated that target ER-α36 may be a strategy for treating ER-negative breast cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Down-Regulation / drug effects
  • Estrogen Receptor alpha / deficiency
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Estrogens / metabolism
  • Female
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • M Phase Cell Cycle Checkpoints / drug effects
  • MicroRNAs / genetics
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness
  • Paclitaxel / pharmacology
  • Signal Transduction / drug effects
  • Transfection

Substances

  • Estrogen Receptor alpha
  • Estrogens
  • MicroRNAs
  • JNK Mitogen-Activated Protein Kinases
  • Paclitaxel