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Tankyrase-1 mRNA expression in bladder cancer and paired urine sediment: preliminary experience

2007; De Gruyter; Volume: 45; Issue: 7 Linguagem: Inglês

10.1515/cclm.2007.133

1437-4331

Stefania Gelmini, Silvia Quattrone, Francesca Malentacchi, Donata Villari, F. Travaglini, Gianluca Giannarini, Alessandro Della Melina, Mario Pazzagli, Giulio Nicita, Cesare Selli, Claudio Orlando,

DNA Repair Mechanisms

The enzyme tankyrase-1 (TNKS-1), a member of the growing family of poly(ADP-ribose) polymerases (PARPs), was identified as a component of the human telomeric complex. PARPs catalyze the formation of long chains of poly(ADP-ribose) onto protein acceptors using NAD(+) as a substrate. TNKS-1 interacts with the telomeric DNA-binding protein TTAGGG repeat-binding factor 1 (TRF1), which is a negative regulator of telomere length. TNKS-1 is a positive regulator of telomere elongation and its activity appears to be upregulated in some human cancers.We evaluated for the first time TNKS-1 mRNA expression by real time RT-PCR in tumor tissue, paired normal mucosa and urine sediment in patients with transitional cell carcinoma (TCC) of the bladder. Samples were collected from 41 consecutive patients, 20 with non-muscle-invasive (pTa-pT1) and 21 with muscle-invasive (>/=pT2) bladder TCC. Results obtained in urine sediment were compared with those from 40 healthy subjects matched for age and sex.In pTa-pT1 tumor tissues, TNKS-1 mRNA levels were significantly higher than in >/=pT2 patients (p /=pT2 patients. In particular, TNKS-1 mRNA levels in urine were elevated in 31/41 patients with a sensitivity of 81% in >/=pT2 tumors and 65% in pTa-pT1 TCC. Of patients with pTa-pT1 tumors, 11 had a recurrence within 18 months after initial transurethral resection. In these patients, urine levels of TNKS-1 mRNA were higher than in non-relapsing patients (p=0.038).In this preliminary study, TNKS-1 mRNA in urine sediment from patients with bladder TCC correlated with tumor stage, and higher preoperative levels were associated with increased risk of early recurrence.