AbstractCaveolae are abundant membrane domain on the cell surface of many mammalian cell types and are implicated in a wide range of physiological processes. The caveolae structural protein caveolin‐1 is often mutated or deregulated in cancer, and cavin family protein serum deprivation response factor‐related gene product that binds to C‐kinase (SRBC) has been found to be epigenetically inactivated in lung, breast, and gastric cancer. Both caveolin‐1 and SRBC have been proposed to function as tumor suppressors. Polymerase 1 and transcript release factor (PTRF) is the essential component for caveolae formation. The regulation of PTRF expression in cancer has not been characterized. We report here that the cavin family protein PTRF, SRBC and serum deprivation response protein were down regulated in breast cancer cell lines and breast tumor tissue. We further show that down‐regulation of PTRF in breast cancer cells was associated with the promoter methylation. As caveolin‐1 and cavin family proteins are required for caveolae formation and function, the reported tumor suppression function of caveolin‐1 and SRBC may be due to the deregulation of caveolae and its down‐stream signaling. Thus, the caveolae is a potential therapeutic target and the expression of cavin family proteins could be a useful prognostic indicator of breast cancer progression. J. Cell. Biochem. 113: 322–328, 2012. © 2011 Wiley Periodicals, Inc.