Caveolin-1 expression is elevated in claudin-low mammary tumor cells

Caveolin-1 expression was evaluated in (1) mammary tumors induced by the transgenic overexpression of the type I insulin-like growth factor receptor (IGF-IR), (2) mammary tumors that became independent of IGF-IR signalling and acquired a claudin-low genotype, (3) two murine mammary epithelial tumor cell lines and (4) two murine mammary claudin-low tumor cell lines.We found that mammary tumors induced by IGF-IR overexpression expressed low levels of caveolin-1 while mammary tumors that became independent of IGF-IR signalling expressed considerably higher levels of caveolin-1. Interestingly, pockets of caveolin-1 positive cells could be observed in some of the IGF-IR-induced mammary tumors and these caveolin-1 positive cells were associated with tumor cells that expressed basal cytokeratins (cytokeratins 5 and 14). This caveolin-1 expression pattern was maintained in the murine mammary tumor cell lines in that the epithelial mammary tumor cell lines expressed little or no caveolin-1 while the claudin-low cell lines expressed caveolin-1.Our model indicates that mammary tumor cells with epithelial characteristics lack caveolin-1 while mesenchymal tumor cells express caveolin-1 suggesting that caveolin-1 may serve as a marker of mammary tumor cells with mesenchymal characteristics such as claudin-low breast tumors.Caveolin-1 (Cav-1) is a member of the caveolin family which consists of Cav-1, Cav-2 and Cav-3. Caveolins function as scaffolding proteins and are found in plasma membrane invaginations known as caveolae. Cav-1 and Cav-2 are co-expressed and found in a number of cell types including endothelial cells, adipocytes, and type I alveolar cells while Cav-3 is expressed in skeletal, cardiac and smooth muscle cells [1-4]. In normal cells caveolins regulate signal transduction, cholesterol metabolism, and vesicular transport.Most of the work performed on Cav-1 in breast cancer has been directed towards the stromal cells. Loss of Cav-1 in stromal cells surrounding breast