Caveolin-1 mutations in human breast cancer: Functional association with estrogen receptor α-positive status

Tianhong Li, Federica Sotgia, Magalis A. Vuolo, Maomi Li, Wan Cai Yang, Richard G. Pestell, Joseph A. Sparano, Michael P. Lisanti

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


A Japanese study reported that up to 16% of breast cancer samples harbor a sporadic mutation within the human Cav-1 gene, namely P132L. To date, however, no studies have examined the United States' population. Here, we developed a novel allele-specific real-time PCR assay to detect the Cav-1 P132L mutation in mammary tumor cells isolated by laser capture microdissection from formalin-fixed paraffin-embedded breast cancer samples. We report that the Cav-1 P132L mutation is present in ∼19% of estrogen receptor α (ERα)-positive breast cancers but not in ERα-negative breast cancers. This is the first demonstration that the P132L mutation is exclusively associated with ERα-positive mammary tumors. We also identified six novel Cav-1 mutations associated with ERα-positive breast cancers (W128Stop, Y118H, S136R, I141T, Y148H, and Y148S). Thus, the overall incidence of Cav-1 mutations in ERα-positive breast cancers approaches 35% (greater than one-third). To mechanistically dissect the functional relationship between Cav-1 gene inactivation and ERα expression, we isolated primary mammary epithelial cells from wild-type and Cav-1-/- mice and cultured them in a three-dimensional system, allowing them to form mammary acinar-like structures. Under conditions of growth factor deprivation, Cav-1-deficient mammary acini displayed increased ERα levels and enhanced sensitivity toward estrogen-stimulated growth, with specific up-regulation of cyclin D1. Finally, we discuss the possibility that sporadic Cav-1 mutations may act as an initiating event in human breast cancer pathogenesis.

Original languageEnglish (US)
Pages (from-to)1998-2013
Number of pages16
JournalAmerican Journal of Pathology
Issue number6
StatePublished - Jun 2006
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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