title: Expression of circadian clock genes and proteins in urothelial cancer is related to cancer-associated genes.
abstract: The purpose of this study was to evaluate invasive and metastatic potential of urothelial cancer by investigating differential expression of various clock genes/proteins participating in the 24 h circadian rhythms and to compare these gene expressions with transcription of other cancer-associated genes.
  
  
  
  Twenty seven paired samples of tumour and benign tissue collected from patients who underwent cystectomy were analysed and compared to 15 samples of normal bladder tissue taken from patients who underwent cystoscopy for benign prostate hyperplasia (unrelated donors). Immunohistochemical analyses were made for clock and clock-related proteins. In addition, the gene-expression levels of 22 genes (clock genes, casein kinases, oncogenes, tumour suppressor genes and cytokeratins) were analysed by real-time quantitative PCR (qPCR).
  
  
  
  Considerable up- or down-regulation and altered cellular distribution of different clock proteins, a reduction of casein kinase1A1 (CSNK1A1) and increase of casein kinase alpha 1 E (CSNK1E) were found. The pattern was significantly correlated with simultaneous up-regulation of stimulatory tumour markers, and a down-regulation of several suppressor genes. The pattern was mainly seen in aneuploid high-grade cancers. Considerable alterations were also found in the neighbouring bladder mucosa.
  
  
  
  The close correlation between altered expression of various clock genes and common tumour markers in urothelial cancer indicates that disturbed function in the cellular clock work may be an important additional mechanism contributing to cancer progression and malignant behaviour.
authors.affiliation: Department of Clinical Science, The Gade Laboratory of Pathology, University of Bergen, Bergen, Norway. Jorunn.Litlekalsoy@k1.uib.no.|Department of Clinical Medicine, Section of Surgery, University of Bergen, Bergen, Norway. Jorunn.Litlekalsoy@k1.uib.no.|Department of Clinical Science, Haukeland University Hospital, N-5021, Bergen, Norway. Jorunn.Litlekalsoy@k1.uib.no.
authors.forename: Jorunn
authors.identifier: 0000-0001-7393-1955
authors.initials: J
authors.lastname: Litlekalsoy
authors.affiliation: Institute of Biomedical Laboratory Sciences and Chemical Engineering, Bergen University College, Bergen, Norway.
authors.forename: Kari
authors.initials: K
authors.lastname: Rostad
authors.affiliation: Department of Clinical Science, The Gade Laboratory of Pathology, University of Bergen, Bergen, Norway.|Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Karl-Henning
authors.initials: KH
authors.lastname: Kalland
authors.affiliation: Department of Clinical Medicine, Section of Surgery, University of Bergen, Bergen, Norway.|Department of Urology, Surgical Clinic, Haukeland University Hospital, Bergen, Norway.
authors.forename: Jens G
authors.initials: JG
authors.lastname: Hostmark
authors.affiliation: Department of Clinical Science, The Gade Laboratory of Pathology, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Ole Didrik
authors.initials: OD
authors.lastname: Laerum
mesh_terms: D000782:Aneuploidy; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014157:Transcription Factors / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium / Q000378:metabolism / Q000473:pathology*
chemical_list: D056925:Circadian Rhythm Signaling Peptides and Proteins; D014157:Transcription Factors
keywords: Casein kinases; Circadian clock genes; Oncogenes; Tumour suppressor genes and cytokeratins