Caveolin in breast cancer

• Published in: Cancer biology & therapy 2004-10, Vol.3 (10), p.931-941
• Main Authors: Bouras, Toula, Lisanti, Michael P., Pestell, Richard G.
• Format: Article
• Language: English
• Subjects: Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cycle; Landes; Organogenesis; Proteins
• ISSN: 1538-4047; 1555-8576
• DOI: 10.4161/cbt.3.10.1147

Caveolin-1 is the principle structural protein of caveolae, sphingolipid and cholesterolrich invaginations of the plasma membrane involved in vesicular trafficking and signal transduction. During caveolae-dependent signaling, caveolin-1 acts as a scaffold protein to sequester and organize multi-molecular signaling complexes involved in diverse cellular activities and as such serves as a paradigm by which numerous disease processes may be affected by ablation or mutation of caveolin-1. The hypothesis that caveolin-1 conveys a tumor/transformation suppressor function in the mammary gland is derived from several independent lines of evidence accumulated by genetic, molecular and clinical approaches. The human caveolin-1 gene maps to a suspected tumor suppressor locus (D7S522/ 7q31.1) frequently deleted in human breast carcinomas. In addition, up to 16% of human breast carcinomas harbor a dominant-negative mutation, P132L in the caveolin-1 gene. Caveolin-1 RNA and protein levels are also downregulated in human primary breast carcinomas and cell lines, with reintroduction of caveolin-1 in vitro sufficient to inhibit numerous tumorigenic properties, including anchorage independent growth and invasiveness. Most recently caveolin-1 knockout mice have provided breakthroughs in understanding the dynamic role of caveolin-1 in the pathogenesis of mammary epithelial cell hyperplasia, tumorigenesis and metastasis in a vivo setting. This review concentrates on recent advances implicating caveolin-1 in breast cancer pathogenesis, with emphasis on the signaling pathways regulated during these processes.