title: Implication of RAF and RKIP genes in urinary bladder cancer.
abstract: RKIP has been shown to regulate the RAS-RAF-MEK-ERK kinase cascade acting as modulator of apoptosis and metastasis in prostate cancer. Our goal was to examine the expression of the RAF (A-RAF, B-RAF and RAF-1) and RKIP genes in urinary bladder cancer. Microarray analysis and qPCR was employed to investigate the expression of RAF and RKIP, in 30 patients with transitional cell carcinoma (TCC) of the urinary bladder vs. the corresponding levels of adjacent normal tissue. Computational analysis was also performed on Gene Expression Omnibus (GEO) datasets, to unravel differences in the expression of RAF or RKIP between tumor and control samples, and between superficial and muscle invasive tumors. Microarray analysis revealed >2-fold expression of BRAF and RKIP in T2, T3, grade III tumors vs. controls. B-RAF over-expression was verified by qPCR in pT1, grade III tumors vs. their normal counterparts (p = 0.016). qPCR revealed a significant RKIP reduction in TCC vs. normal tissue (p = 0.002 and p < 0.001 for T1, grade II and Ta-T1, grade III, respectively); All RAF genes were positively correlated among each other (A-RAF/B-RAF, p = 0.003; A-RAF/RAF-1, p < 0.001; B-RAF/RAF-1, p = 0.050), whereas B-RAF was negatively correlated with RKIP in TCC (p = 0.050). Further computational analysis revealed different expression profiles for the genes of interest, among muscle invasive carcinomas, superficial TCCs, cystectomy specimens and normal tissue. The reduced RKIP mRNA levels in TCC and the elevated levels of B-RAF in pT1, grade III tumors vs. normal tissue, corroborate that these genes are involved in the pathogenesis of urinary bladder cancer.
authors.affiliation: Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion, 71110 Crete, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Zaravinos
authors.forename: Maria
authors.initials: M
authors.lastname: Chatziioannou
authors.forename: George I
authors.initials: GI
authors.lastname: Lambrou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Boulalas
authors.forename: Dimitris
authors.initials: D
authors.lastname: Delakas
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D048490:raf Kinases / Q000235:genetics*
chemical_list: C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D012333:RNA, Messenger; D048490:raf Kinases