This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Myers-Irvin, J. M. Articles by Getzenberg, R. H. Search for Related Content PubMed PubMed Citation Articles by Myers-Irvin, J. M. Articles by Getzenberg, R. H.

Mechanistic Analysis of the Role of BLCA-4 in Bladder Cancer Pathobiology

Departments of Urology, Pathology, and Pharmacology, University of Pittsburgh and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania

Requests for reprints: Robert H. Getzenberg, Brady Urological Institute, Johns Hopkins Hospital, Marburg 121, 600 North Wolfe Street, Baltimore, MD 21287. Fax: 412-623-3904; E-mail: rgetzen1{at}jhmi.edu.

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-1 (IL-1), 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.

This article has been cited by other articles:

				T. A. Dunn, S. Chen, D. A. Faith, J. L. Hicks, E. A. Platz, Y. Chen, C. M. Ewing, J. Sauvageot, W. B. Isaacs, A. M. De Marzo, et al. A Novel Role of Myosin VI in Human Prostate Cancer Am. J. Pathol., November 1, 2006; 169(5): 1843 - 1854. [Abstract] [Full Text] [PDF]