BACKGROUND: 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. METHODS: 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. RESULTS: In pTa-pT1 tumor tissues, TNKS-1 mRNA levels were significantly higher than in >/=pT2 patients (p<0.0001). In urine sediment from TCC patients, independent of tumor stage, TNKS-1 mRNA levels were significantly higher than in healthy controls, with maximal levels in >/=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). CONCLUSIONS: 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.
BACKGROUND: 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 humancancers. METHODS: 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. RESULTS: In pTa-pT1 tumor tissues, TNKS-1 mRNA levels were significantly higher than in >/=pT2 patients (p<0.0001). In urine sediment from TCC patients, independent of tumor stage, TNKS-1 mRNA levels were significantly higher than in healthy controls, with maximal levels in >/=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). CONCLUSIONS: 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.
Authors: Amit Nathubhai; Pauline J Wood; Matthew D Lloyd; Andrew S Thompson; Michael D Threadgill Journal: ACS Med Chem Lett Date: 2013-10-15 Impact factor: 4.345
Authors: Angeline S Andrew; Jiang Gui; Ting Hu; Asaf Wyszynski; Carmen J Marsit; Karl T Kelsey; Alan R Schned; Sam A Tanyos; Eben M Pendleton; Rebecca M Ekstrom; Zhongze Li; Michael S Zens; Mark Borsuk; Jason H Moore; Margaret R Karagas Journal: BJU Int Date: 2014-03-26 Impact factor: 5.588
Authors: Oluf Dimitri Røe; Adam Szulkin; Endre Anderssen; Arnar Flatberg; Helmut Sandeck; Tore Amundsen; Sten Even Erlandsen; Katalin Dobra; Stein Harald Sundstrøm Journal: PLoS One Date: 2012-08-08 Impact factor: 3.240
Authors: Xiao-Hong Tian; Wei-Jian Hou; Yan Fang; Jun Fan; Hao Tong; Shu-Ling Bai; Qu Chen; He Xu; Yan Li Journal: J Exp Clin Cancer Res Date: 2013-12-05