Disturbance of circadian gene expression in endometrial cancer: detection by real-time quantitative RT-PCR.
Circadian genes control the daily changes of the circadian rhythms in a variety of physiological processes, which in turn regulate many functions in the human body. Disruption of circadian rhythms can have a profound influence on our well-being. We established a set of PCR primers and fluorescent probes to analyze the mRNA levels of nine different circadian genes, and used immunohistochemical methods to study four important circadian proteins in 35 endometrial cancers and their paired non-cancerous tissues. Of these, 13 cases showed reduced expression in all nine circadian genes in the cancerous tissues relative to the paired non-cancerous tissues; the remaining cases showed similar reduced expression in 4-8 of the genes analyzed. Conversely, 3 non-cancerous tissues showed reduced expression in all nine circadian genes in comparison with their respective adjacent cancerous tissues, whereas 6 other non-cancerous tissues showed reduced expression in 6-8 of the circadian genes. These results were also confirmed by immunohistochemical study. Expression of the circadian genes is perturbed in endometrial cancer. Based on these results, we suggest that different circadian rhythms occur in endometrial cancer and non-cancerous tissues. Our results may provide the molecular basis for chronotherapy of endometrial cancer.
Shih
Hong-Chang
HC
Department of Molecular Medicine, China Medical University Hospital, 2 Yuh Der Road, Taichung, Taiwan.
Choo
Kong-Bung
KB
Chang
Tien-Jye
TJ
Yang
Ming-Yu
MY
Shih
Mu-Chin
MC
Yeh
Kun-Tu
KT
Liu
Ta-Chih
TC
Lin
Shung-Feng
SF
Chang
Jan-Gowth
JG
D000328:Adult; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539022:PER1 protein, human; C421902:PER2 protein, human; C512644:PER3 protein, human; C539023:Per1 protein, mouse; C512645:Per3 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D014157:Transcription Factors