Differential effects of Nucleostemin suppression on cell cycle arrest and apoptosis in the bladder cancer cell lines 5637 and SW1710

Abstract

The Nucleostemin (NS) gene encodes a nucleolar protein enriched in adult and embryonic stem cells. NS is thought to regulate cancer cell proliferation, but the mechanisms involved are poorly understood. In this study, we have investigated the role of NS in bladder cancer. Expression of NS was determined by quantitative reverse transcription-polymerase chain reaction in bladder carcinoma cell lines and in normal uro-epithelial cell cultures. We used an RNAi strategy to investigate the function of NS in two selected carcinoma cell lines. High NS expression was found in most bladder carcinoma cell lines and normal uro-epithelial cells. Knockdown of NS expression induced a severe decline in cell proliferation in 5637 and SW1710 cell lines, both with mutant p53. Apoptosis was more strongly enhanced in 5637 cells lacking RB1 than in SW1710 cells lacking p16(INK4A). Moreover, NS-siRNA-treated 5637 cells accumulated mainly in G(2)/M, whereas SW1710 cells arrested in G(0)/G(1). Our data indicate that NS expression is necessary for cell proliferation and evasion of apoptosis in bladder cancer cells, independent of its effect on p53. Also, we speculate that the precise effect of NS on cell cycle regulation may relate to functional status of RB1 and CDKN2A/p16(INK4A).