Expression of the circadian clock genes Per1 and Per2 in sporadic and familial breast tumors.
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 and the clock proteins Per1 and 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 and Per2 in both sporadic and familial primary breast tumors and normal breast tissues using real-time polymerase chain reaction. Significantly decreased levels of Per1 were observed between sporadic tumors and normal samples (P < .00001), as well as a further significant decrease between familial and sporadic breast tumors for both Per1 (P < .00001) and Per2 (P < .00001). Decreased Per1 was also associated with estrogen receptor negativity (53% vs 15%, P = .04). These results suggest a role for both Per1 and Per2 in normal breast function and 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 and on the ability of cells to undergo apoptosis, potentially promoting carcinogenesis.
Winter
Sherry L
SL
Fred A. Litwin Center for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Bosnoyan-Collins
Lucine
L
Pinnaduwage
Dushanthi
D
Andrulis
Irene L
IL
D019313:BRCA1 Protein / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002940:Circadian Rhythm / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis*; D056950:Period Circadian Proteins; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis*
D019313:BRCA1 Protein; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539022:PER1 protein, human; C421902:PER2 protein, human; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D014157:Transcription Factors