Sperm associated antigen 9 plays an important role in bladder transitional cell carcinoma. PLoS One 2013;8(12):e81348
Date
12/19/2013Pubmed ID
24349057Pubmed Central ID
PMC3857194DOI
10.1371/journal.pone.0081348Scopus ID
2-s2.0-84892589073 (requires institutional sign-in at Scopus site) 32 CitationsAbstract
BACKGROUND: Majority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC) which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9) in bladder TCC.
METHODOLOGY AND FINDINGS: We examined SPAG9 expression and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines were assessed for SPAG9 expression. In addition, we investigated the effect of SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells) was found to be significantly associated with superficial non-muscle invasive stage (P = 0.042) and low grade tumors (P = 0.002) suggesting SPAG9 putative role in early spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of patients found positive for SPAG9 expression. All four bladder cancer cell lines revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells resulted in induction of G0-G1 arrest characterized by up-regulation of p16 and p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular growth, and migration and invasion ability of cancer cells in vitro.
CONCLUSIONS: Collectively, our data in clinical specimens indicated that SPAG9 is potential biomarker and therapeutic target for bladder TCC.
Author List
Kanojia D, Garg M, Saini S, Agarwal S, Parashar D, Jagadish N, Seth A, Bhatnagar A, Gupta A, Kumar R, Lohiya NK, Suri AAuthor
Deepak Parashar PhD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAdult
Biomarkers, Tumor
Carcinoma, Transitional Cell
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Female
Humans
In Vitro Techniques
Male
Middle Aged
Urinary Bladder Neoplasms
