OBJECTIVE: To investigate the role of fatty acid synthase (FASN) in bladder transitional cell carcinoma (BTCC).
METHODS: FASN expression was investigated in non-muscle-invasive BTCC tissue specimens by immunohistochemistry and BTCC cell lines by Western blot. After treatment with FASN-siRNA or FASN inhibitor cerulenin (Cer), the proliferation and apoptosis of BTCC cell lines 5637 and 253 J were determined by cell counting Kit-8 (CCK8) assay and flow cytometry respectively. The expression of p-AKT, cyclin D1 (CCND1), and apoptosis-related proteins were detected by Western blot.
RESULTS: High levels of FASN expression were observed in 59% (32/54) of non-muscle-invasive BTCC tissue specimens, and FASN expression was associated with histologic grade (P < .05) and recurrence (P < .05). FASN expression was high in 6 BTCC cell lines. FASN inhibitor Cer and FASN-siRNA produced the increased apoptosis and decreased proliferation of bladder cancer cells, and caused inactivity of AKT and downregulation of CCND1. Furthermore, treatment of BTCC cell lines with Cer resulted in apoptosis via the caspase-dependent pathway involving inactivation of antiapoptotic bcl-2 protein.
CONCLUSION: Our data suggest that FASN plays an important role in BTCC development. Targeting FASN may be a new therapeutic strategy for BTCC.
Written by:
Jiang B, Li EH, Lu YY, Jiang Q, Cui D, Jing YF, Xia SJ. Are you the author?
Department of Urology, The Affiliated First People's Hospital of Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Reference: Urology. 2012 Aug;80(2):484.e9-484.e15.
doi: 10.1016/j.urology.2012.02.046
PubMed Abstract
PMID: 22554590
UroToday.com Investigative Urology Section