Correlated downregulation of estrogen receptor beta and the circadian clock gene Per1 in human colorectal cancer
2009
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 G2 and G3 colorectal tumors revealed a decrease of Per1 mRNA compared with paired NM (G2: 0.52-fold; P = n.s. and G3: 0.48-fold; P = 0.03). A significant gender specific difference of Per1 expression was observed in G2 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 G2 tumors of male patients (1.63-fold, P = 0.01). The expression of ER-beta was significantly decreased in G2 and G3 tumors (G2: 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 G2 tumors might suggest a gender-specific, distinctive role of the cellular clock in colorectal tumorigenesis. © 2009 Wiley-Liss, Inc.
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