期刊
CANCER RESEARCH
卷 65, 期 16, 页码 7145-7150出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-05-1142
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资金
- NCI NIH HHS [R01 CA82522] Funding Source: Medline
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 BLCA4. Up-regulated genes included interleukin-1 alpha (IL-1 alpha), 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.
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