Tumor suppressor role of KiSS-1 in bladder cancer: loss of KiSS-1 expression is associated with bladder cancer progression and clinical outcome.
The expression profiles of nine bladder cancer cell lines were compared against a pool containing equal total RNA quantities of each of them. Lower expression of KiSS-1 was revealed in cells derived from the most advanced bladder tumors. When comparing 15 primary bladder tumors versus a pool of four bladder cancer cell lines, lower transcript levels of KiSS-1 were observed in the invasive bladder carcinomas as compared to superficial tumors. KiSS-1 expression ratios provided prognostic information. The expression pattern of KiSS-1 transcripts was analyzed using in situ hybridization in nine bladder cancer cells, paired normal urothelium and bladder tumor samples (n = 25), and tissue microarrays of bladder tumors (n = 173). We observed complete loss of KiSS-1 in all invasive tumors under study as compared to their respective normal urothelium. The expression of KiSS-1 was found to be significantly associated with histopathological stage. Patients with lower KiSS-1 expression showed a direct correlation with overall survival in a subset of bladder tumors whose follow-up was available (n = 69). We did not observe any significant differential KiSS-1 expression along cell cycle by sorting analysis. A potential tumor suppressor role in bladder cancer was revealed for KiSS-1. Moreover, it showed predictive value by identifying patients with poor outcome.
Sanchez-Carbayo
Marta
M
Division of Molecular Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA. sanchezm@mskcc.org
Capodieci
Paola
P
Cordon-Cardo
Carlos
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D016161:Genes, Retinoblastoma; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D017403:In Situ Hybridization; D059648:Kisspeptins; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics*; D012907:Smoking; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
C106628:KISS1 protein, human; D059648:Kisspeptins; D011506:Proteins; D025521:Tumor Suppressor Proteins