Expression of the Circadian Clock Genes Pert, Per2 in Sporadic, Familial Breast Tumors 1

There is a growing body of evidence implicating aberrant circadian clock expression in the development of cancer. Based on our initial experiments identifying a putative interaction between BRCA1, the clock proteins Per1, Per2, as well as the reported involvement of the circadian clock in the development of cancer, we have performed an expression analysis of the circadian clock genes Per1, Per2 in both sporadic, familial primary breast tumors, normal breast tissues using real-time polymerase chain reaction. Significantly decreased levels of Per1 were observed between sporadic tumors, normal samples (P < .00001), as well as a further significant decrease between familial, sporadic breast tumors for both Per1 (P < .00001), Per2 (P < .00001). Decreased Per1 was also associated with estrogen receptor negativity (53% vs 15%, P = .04). These results suggest a role for both Perl, Per2 in normal breast function, show for the first time that deregulation of the circadian clock may be an important factor in the development of familial breast cancer. Aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle, on the ability of cells to undergo apoptosis, potentially promoting carcinogenesis.