Mechanistic analysis of the role of BLCA-4 in bladder cancer pathobiology.
Analysis of alterations in nuclear structure associated with bladder cancer has revealed specific changes associated with the disease. This includes the identification of six bladder cancer-specific proteins and the successful development of urine-based immunoassays for the detection of two of these biomarkers, BLCA-1 and BLCA-4. The purpose of this study is to examine the functional aspects of BLCA-4 and its potential role in bladder cancer pathobiology. Sequence analysis of BLCA-4 reveals that it is a member of the ETS transcription factor family and that it seems to associate with transcription factors. To examine the effects of this protein, the gene encoding BLCA-4 was stably transfected into human urothelial cells. BLCA-4 expression was confirmed by both PCR and Western blot analysis. BLCA-4 overexpressing clones exhibit a 4.3-fold greater proliferation rate than vector only controls or untransfected cells. Microarray analysis comparing gene expression patterns between overexpressing clones and vector only controls revealed that numerous genes were up-regulated in cells that overexpress BLCA-4. Up-regulated genes included interleukin-1alpha (IL-1alpha), IL-8, and thrombomodulin, and the protein expression of these genes was confirmed by immunoblots. This information has provided a potential model of BLCA-4 action. Overexpression of BLCA-4 seems to increase the growth rate in cells and also causes cells to express a more tumorigenic phenotype.
Myers-Irvin
Julie M
JM
Department of Urology, University of Pittsburgh and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
Van Le
Thu-Suong
TS
Getzenberg
Robert H
RH
D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D048708:Cell Growth Processes / Q000235:genetics; D002461:Cell Line, Transformed; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins
D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C413062:BLCA-4 protein, human; D009363:Neoplasm Proteins