Correlated downregulation of estrogen receptor beta and the circadian clock gene Per1 in human colorectal cancer.
There is a growing body of evidence that disturbed circadian clock gene expression is associated with tumor development and tumor progression. Based on our initial experiments demonstrating decreased period 1 (Per1) expression in colon cancer, we evaluated clock gene and estrogen receptor (ER) alpha/beta expression in colon cancer cells of primary colorectal tumors and adjacent normal colon mucosa (NM) by real-time RT-PCR. Analysis of gene expression in G(2) and G(3) colorectal tumors revealed a decrease of Per1 mRNA compared with paired NM (G(2): 0.52-fold; P = n.s. and G(3): 0.48-fold; P = 0.03). A significant gender specific difference of Per1 expression was observed in G(2) tumors as compared with NM (female: 0.38-fold; P = 0.004 vs. male: 0.73-fold; P = n.s.). Expression of CLOCK was significantly elevated in G(2) tumors of male patients (1.63-fold, P = 0.01). The expression of ER-beta was significantly decreased in G(2) and G(3) tumors (G(2): 0.32-fold; P = 0.003 and 0.27; P = 0.001). No significant gender specific differences of ER-beta reduction in tumors were observed. A significant correlation between the decrease of Per1 and ER-beta in colorectal tumors (r = 0.61; P < 0.001) was found. No changes in gene expression were detected for ER-alpha and Per2. Our data demonstrate a correlated decrease of Per1 and ER-beta in colorectal tumors, mediated probably by epigenetic mechanisms. The observed gender differences in the expression of CLOCK and Per1 in G(2) tumors might suggest a gender-specific, distinctive role of the cellular clock in colorectal tumorigenesis.
Mostafaie
Nazanin
N
Department of Clinical Chemistry, Donauspital, Vienna, Austria.
Kállay
Enikö
E
Sauerzapf
Elisabeth
E
Bonner
Elisabeth
E
Kriwanek
Stefan
S
Cross
Heide S
HS
Huber
Klaus Roland
KR
Krugluger
Walter
W
D002940:Circadian Rhythm; D015179:Colorectal Neoplasms / Q000235:genetics*; D015536:Down-Regulation; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D056950:Period Circadian Proteins; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D047629:Estrogen Receptor beta; D047908:Intracellular Signaling Peptides and Proteins; C539022:PER1 protein, human; D056950:Period Circadian Proteins; D012333:RNA, Messenger