Caveolin-1 in breast cancer.
Caveolin-1 is the principal structural protein of caveolae, sphingolipid and cholesterol-rich 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.
Bouras
Toula
T
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, Washington, DC 20057-1468, USA.
Lisanti
Michael P
MP
Pestell
Richard G
RG
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D051242:Caveolin 1; D022461:Caveolins / Q000502:physiology*; D005260:Female; D006801:Humans
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins