title: Altered expression of the clock gene machinery in kidney cancer patients.
abstract: OBJECTIVE
  Kidney cancer is associated with alteration in the pathways regulated by von Hippel-Lindau protein and hypoxia inducible factor α. Tight interrelationships have been evidenced between hypoxia response pathways and circadian pathways. The dysregulation of the circadian clock circuitry is involved in carcinogenesis. The aim of our study was to evaluate the clock gene machinery in kidney cancer.
  
  
  METHODS
  mRNA expression levels of the clock genes ARNTL1, ARNTL2, CLOCK, PER1, PER2, PER3, CRY1, CRY2, TIMELESS, TIPIN and CSNK1E and of the clock controlled gene SERPINE1 were evaluated by DNA microarray assays and by qRT-PCR in primary tumor and matched nontumorous tissue collected from a cohort of 11 consecutive kidney cancer patients.
  
  
  RESULTS
  In kidney tumor tissue, we found down-regulation of PER2 (median=0.658, Q1-Q3=0.562-0.744, P<0.01), TIMELESS (median=0.705, Q1-Q3=0.299-1.330, P=0.04) and TIPIN (median=0.556, Q1-Q3=0.385-1.945, P=0.01), up-regulation of SERPINE1 (median=1.628, Q1-Q3=0.339-4.071, P=0.04), whereas the expression of ARNTL2 (median=0.605, Q1-Q3=0.318-1.738, P=0.74) and CSNK1E (median=0.927, Q1-Q3=0.612-2.321, P=0.33) did not differ. A statistically significant correlation was evidenced between mRNA levels of PER2 and CSNKIE (r=0.791, P<0.01), PER2 and TIPIN (r=0.729, P=0.01), PER2 and SERPINE1 (r=0.704, P=0.01), TIMELESS and TIPIN (r=0.605, P=0.04), TIMELESS and CSNKIE (r=0.637, P=0.03), TIPIN and CSNKIE (r=0.940, P<0.01).
  
  
  CONCLUSIONS
  In kidney cancer, the circadian clock circuitry is deregulated and the altered expression of the clock genes might be involved in disease onset and progression.
authors.affiliation: Division of Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute and Regional General Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. g.mazzoccoli@tin.it
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Mazzoccoli
authors.forename: Ada
authors.initials: A
authors.lastname: Piepoli
authors.forename: Massimo
authors.initials: M
authors.lastname: Carella
authors.forename: Anna
authors.initials: A
authors.lastname: Panza
authors.forename: Valerio
authors.initials: V
authors.lastname: Pazienza
authors.forename: Giorgia
authors.initials: G
authors.lastname: Benegiamo
authors.forename: Orazio
authors.initials: O
authors.lastname: Palumbo
authors.forename: Elena
authors.initials: E
authors.lastname: Ranieri
mesh_terms: D056926:CLOCK Proteins / Q000096:biosynthesis / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D015331:Cohort Studies; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D056926:CLOCK Proteins