COX-2 localization within plasma membrane caveolae-like structures in human lobular intraepithelial neoplasia of the breast

Virchows Arch. 2007 Dec;451(6):1039-45. doi: 10.1007/s00428-007-0506-4. Epub 2007 Sep 13.

Abstract

Cyclooxygenase-2 (COX-2) is highly expressed in human intraepithelial neoplasia of the breast and takes part in the molecular pathway implicated in progression of breast cancer. Recently, we demonstrated that COX-2 protein is mainly located in plasma membrane of lobular intraepithelial neoplasia (LIN) cells suggesting a localization in caveolae-like structures. The aim of the present study is to establish subcellular locations of COX-2 and its colocalization with caveolin-1 (CAV-1) to caveolae structures in LIN. To establish a relationship between COX-2 and CAV-1, 39 LINs were studied by immunohistochemistry and confocal microscopy analysis. COX-2 and CAV-1 expression was observed respectively in 79.5 and in 94.9% of LIN studied. A positive correlation was found between membrane COX-2 staining pattern and CAV-1 expression, while no correlation was found between cytoplasm COX-2 staining pattern and CAV-1. Confocal analysis showed that COX-2 localized to plasma membrane was strictly associated to CAV-1 suggesting that an amount of COX-2 protein is placed in caveolae-like structures. Our results show that COX-2 is localized within caveolae compartment and colocalized with CAV-1 protein in LIN lesions. Because caveolae are rich in signaling molecules, this COX-2 compartment may play an important role in diverse breast cancer carcinogenesis processes.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / enzymology*
  • Carcinoma in Situ / enzymology*
  • Carcinoma, Lobular / enzymology*
  • Caveolae / enzymology*
  • Caveolin 1 / metabolism*
  • Cyclooxygenase 2 / metabolism*
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged

Substances

  • Biomarkers, Tumor
  • CAV1 protein, human
  • Caveolin 1
  • Cyclooxygenase 2
  • PTGS2 protein, human