Circadian variation in expression of G1 phase cyclins D1 and E and cyclin-dependent kinase inhibitors p16 and p21 in human bowel mucosa

• Published in: World journal of gastroenterology : WJG Vol. 12; no. 13; pp. 2109 - 2114
• Main Authors: Griniatsos, John, Michail, Othon P, Theocharis, Stamatios, Arvelakis, Antonios, Papaconstantinou, Ioannis, Felekouras, Evangelos, Pikoulis, Emmanouel, Karavokyros, Ioannis, Bakoyiannis, Chris, Marinos, George, Bramis, John, Michail, Panayiotis O
• Format: Journal Article
• Language: English
• Published: United States 1st Department of Surgery, Medical School, University of Athens, Greece%Department of Forensic Medicine and Toxicology, Medical School, University of Athens, Greece 07-04-2006; Baishideng Publishing Group Co., Limited
• Subjects: Aged; Circadian Rhythm; Colon - chemistry; Cyclin D1 - analysis; Cyclin E - analysis; Cyclin-Dependent Kinase Inhibitor p16 - analysis; Cyclin-Dependent Kinase Inhibitor p21 - analysis; Female; G1 Phase; G1位相周期蛋白; Humans; Immunohistochemistry; Intestinal Mucosa - chemistry; Male; Middle Aged; Rapid Communication; 抑制剂; 生理节奏; 肠黏膜; Cell proliferation; G1 phase proteins; Circadian rhythm; CDK inhibitors
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v12.i13.2109

AIM： To evaluate whether the cellular proliferation rate in the large bowel epithelial cells is characterized by circadian rhythm. METHODS： Between January 2003 and December 2004, twenty patients who were diagnosed as suffering from primary, resectable, non-metastatic adenocarcinoma of the lower rectum, infiltrating the sphincter mechanism, underwent abdominoperineal resection, total mesorectal excision and permanent left iliac colostomy. In formalinfixed and paraffin-embedded biopsy specimens obtained from the colostomy mucosa every six hours （00：00, 06：00, 12：00, 18：00 and 24：00）, we studied the expression of G1 phase cyclins （D1 and E） as well as the expression of the G1 phase cyclin-dependent kinase （CDK） inhibitors p16 and p21 as indicators of cell cycle progres- sion in colonic epithelial cells using immunohistochemical methods. RESULTS： The expression of both cyclins showed a similar circadian fashion obtaining their lowest and highest values at 00：00 and 18：00, respectively （P〈 0.001）. A circadian rhythm in the expression of CDK inhibitor proteins p16 and p21 was also observed, with the lowest levels obtained at 12：00 and 18：00 （P〈0.001）, respectively. When the complexes cyclins D1-p21 and E-p21 were examined, the expression of the cyclins was adversely correlated to the p21 expression throughout the day. When the complexes the cyclins D1-p16 and E-p16 were examined, high levels of p16 expression were correlated to low levels of cyclin expression at 00：00, 06：00 and 24：00. Meanwhile, the highest expression levels of both cyclins were correlated to high levels of p16 expression at 18：00. CONCLUSION： Colonic epithelial cells seem to enter the G1 phase of the cell cycle during afternoon （between 12：00 and 18：00） with the highest rates obtained at 18：00. From a clinical point of view, the present results suggest that G1-phase specific anticancer therapies in afternoon might maximize their anti-tumor effect while minimizing toxicity.