P27 and pAKT Expression in BRCA1-associated and sporadic breast tumors

Abstract

9609 Background: P27 is a tumor suppressor gene that inhibits the cyclin E/CDK2 complex. Somatic loss of p27 function may occur as a result of decreased p27 expression or as a result of nuclear exclusion of the p27 protein. Nuclear exclusion of p27 results from phosphorylation of the p27 protein. This phosphorylation is effected by activated/phosphorylated AKT (protein kinase B). Recent evidence suggests that the BRCA1 protein transactivates expression of p27. Thus, loss of BRCA1 function during carcinogenesis, is expected to be associated with decreased p27 expression. Prior studies have reported p27 loss in 40–55% of unselected breast tumors. Two series have failed to identify a difference in the rate of p27 loss between BRCA1-associated and sporadic tumors. Methods: Using a comparative case series design, we have examined p27 protein expression in the paraffin-embedded, breast tumors of 54 age-matched, BRCA1/sporadic breast tumor pairs. Conclusion: BRCA1-associated tumors are more frequently associated with p27 downregulation than sporadic breast tumors in this series. Staining for activated AKT does not differ between BRCA1-associated and unselected breast tumors, nor do differences in AKT activation appear to be associated with decreased p27 nuclear staining in BRCA1-associated tumors. These findings are consistent with the hypothesis that loss of BRCA1 function is directly responsible for loss of p27 nuclear expression. No significant financial relationships to disclose.