Our laboratory has been investigating the role of caveolin-1, a caveolin isoform that is expressed in most cell types with the exception of striated muscle cells, in cellular senescence and cancer. Senescent human diploid fibroblasts have been shown to express higher levels of caveolin-1, as compared to younger human diploid fibroblasts. We have recently generated caveolin-1 transgenic mice. Interestingly, mouse embryonic fibroblasts over-expressing caveolin-1, derived from this mouse model, display a premature senescent phenotype. Taken together, these results indicate that caveolin-1 may have a central role in the signaling events that lead to cellular senescence. As a consequence, caveolin-1 may possess tumor suppressor properties. Several independent data support the idea that caveolin-1 is a tumor suppressor protein: i) caveolin-1 expression is down-regulated in a variety of human cancers; ii) down-regulation of caveolin-1 is sufficient to transform fibroblasts in culture; iii) the caveolin-1 gene is localized to a suspected tumor suppressor locus (D7S522; 7q31.1), a known fragile site (FRA7G) that is deleted in many types of cancer; iv) a common sporadic mutation in the caveolin-1 gene has been identify in human breast cancer patients; e) loss of caveolin-1 expression leads to mammary epithelial cell hyperplasia in normal mice, and accelerates the development of dysplastic mammary lesions in tumor-prone transgenic mice.