Expression of cell cycle regulatory factors hus1, gadd45a, rb1, cdkn2a and mre11a correlates with expression of clock gene per2 in human colorectal carcinoma tissue.
Deregulated expression of clock gene per2 has previously been associated with progression of cancer. The aim of the present study was to identify genes related to per2 expression and involved in cell cycle control. Patients surgically treated for colorectal carcinoma with up-regulated and down-regulated per2 expression in cancer versus adjacent tissue were studied. Total RNA from cancer tissue of these patients was used to specify genes associated with altered per2 expression using the Human Cell Cycle RT(2) profiler PCR array system. We identified seven genes positively correlated (hus1, gadd45α, rb1, cdkn2a, cdk5rp1, mre11a, sumo1) and two genes negatively correlated (cdc20, birc5) with per2 expression. Expression of these seven genes was subsequently measured by real time PCR in all patients of the cohort. Patients were divided into three groups according to TNM classification. We observed an increase in gene expression in cancer tissue compared to adjacent tissue in the first group of patients in all genes measured. Expression of genes positively associated with per2 gene expression was dependent on tumor staging and changes were observed preferentially in cancer tissue. For genes negatively associated with per2 expression we also detected changes in expression dependent on tumor staging. Expression of cdc20 and birc5 was increasing in the proximal tissue and decreasing in the cancer tissue. These results implicate functional involvement of per2 in the process of carcinogenesis via newly uncovered genes. The relevancy of gene expression for determination of diagnosis and prognosis should be considered in relation to tumor staging.
Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University Bratislava, Mlynska dolina B-2, 842 15, Bratislava, Slovak Republic.
Mária
M
Štorcelová
Marián
M
Vicián
Richard
R
Reis
Michal
M
Zeman
Iveta
I
Herichová
D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000076228:MRE11 Homologue Protein; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics*; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D016160:Retinoblastoma Protein; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C549605:HUS1 protein, human; C121766:MRE11 protein, human; C421902:PER2 protein, human