Balance between SIRT1 and DBC1 expression is lost in breast cancer

Abstract

SIRT1 (silent mating-type information regulation 2 homologue 1)-mediated cellular resistance to various stresses is negatively regulated by deleted in breast cancer 1 (DBC1), which was originally reported to be deleted in breast cancer. However, the suggested functions of SIRT1 as a potential tumor promoter and of DBC1 as a potential tumor suppressor have been challenged by observations of their respective down- and up-regulation in various cancers. The aim of the present study was to simultaneously evaluate the expression levels of SIRT1 and DBC1 in the normal and tumor breast tissues from 28 breast cancer patients and to determine correlations with clinicopathological variables. SIRT1 and DBC1 expression was higher in tumor tissues than in matched normal tissues at the protein level, but not at the transcriptional level. Overexpression of SIRT1 and DBC1 in tumor tissue was correlated with favorable and unfavorable clinicopathological factors, suggesting their pleiotropic functions as a potential tumor promoter and tumor suppressor in tumorigenesis. Interestingly, although the overall expression of SIRT1 and DBC1 increased in tumor breast tissues, the correlation between SIRT1 and DBC1 expression was weaker in tumor tissue than in normal tissue. This suggests that the negative regulation of SIRT1 by DBC1 may retard tumorigenesis in breast tissue. Therefore, the correlation between SIRT1 and DBC1 is a potential prognostic indicator in breast cancer.