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

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.

Nuclear co-localization and functional interaction of COX-2 and HIF-1α characterize bone metastasis of human breast carcinoma

“…In primary lobular and ductal mammary tumors, COX-2 is present in plasma-membrane caveolae and cytosol, respectively [39], without the nuclear and perinuclear localization observed by us in bone metastasis.…”

Caveolin-1 expression in human breast lobular cancer progression

“…Furthermore, our group recently demonstrated the expression of Cav-1 protein in a large portion of human lobular intraepithelial neoplasia of the breast. 21 Analysing Cav-1 expression in these three population, no significant differences were found between lobular intraepithelial neoplasia lesion with and without invasive component and between invasive lobular carcinoma with and without lobular intraepithelial neoplasia component. These data suggest that, at least for Cav-1, there is no association between Cav-1 expression in lobular intraepithelial neoplasia lesion and in the adjacent invasive lobular carcinoma.…”

“…This antibody has been used and validated previously by our group and by others. 21,23,24 Sections were incubated with LSAB2 (Dakocytomation). 3-3 0 -diaminobenzidine was used for colour development and haematoxylin was used for counterstaining.…”

“…Furthermore, our group recently demonstrated the expression of Cav-1 protein in a large portion of human lobular intraepithelial neoplasia of the breast. 21 In the present study, the Cav-1 expression was evaluated in normal lobular epithelial cells and in the human lobular neoplasia spectrum (lobular intraepithelial neoplasia, invasive lobular cancer) with the aim to comprehensively examine differences of Cav-1 expression in human lobular neoplasia progression.…”

Post-translational regulation of COX2 activity by FYN in prostate cancer cells

“…Here we have investigated the possibility that FYN, found in complex with COX2, is capable to regulate the enzyme activity. Since it has been reported that COX2 and FYN both are localized in caveolae like structures in some cancer cells [36, 37], it is possible that caveolae is one of cellular comparmtent where FYN is capable to regulate COX2 activity.…”