The New Immortalized Uroepithelial Cell Line HBLAK Contains Defined Genetic Aberrations Typical of Early Stage Urothelial Tumors
| العنوان: | The New Immortalized Uroepithelial Cell Line HBLAK Contains Defined Genetic Aberrations Typical of Early Stage Urothelial Tumors |
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| المؤلفون: | Harald Rieder, Wolfgang A. Schulz, Artur Brandt, Günter Niegisch, Margaretha A. Skowron, Stefanie Stepanow, Evangelia A. Koutsogiannouli, Maria Pinkerneil, Michèle J. Hoffmann |
| المصدر: | Bladder Cancer (Amsterdam, Netherlands) |
| بيانات النشر: | IOS Press, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Research Report, p53, 0301 basic medicine, Telomerase, Urothelial Cell, Urology, Biology, telomerase, medicine.disease_cause, cell culture model, normal urothelial cells, CDKN2A, 03 medical and health sciences, 0302 clinical medicine, urothelial differentiation, medicine, Mutation, Cell cycle, 030104 developmental biology, Oncology, Cell culture, 030220 oncology & carcinogenesis, Cancer research, bladder cancer, Carcinogenesis, Immortalised cell line, Immortalization |
| الوصف: | Background: Cell culture models of normal urothelial cells are important for studying differentiation, disease mechanisms and anticancer drug development. Beyond primary cultures with their limitations in lifespan, interindividual heterogeneity and supply, few conditionally immortalized cell lines with limited applicability due to partial transformation or impaired differentiation capacity are available. We describe characteristics of the new spontaneously immortalized cell line HBLAK derived from a primary culture of uroepithelial cells. Objective: To characterize utility and limitations of HBLAK cells as an urothelial cell culture model. Methods: Differentiation markers were investigated by immunofluorescence and RT-PCR, genetic changes by standard karyotyping, array-CGH, PCR, RT-PCR and exome sequencing; expression of p53 and p21 by Western blotting. Results: HBLAK cells proliferated for >50 passages without senescing. They expressed cytokeratins of basal urothelial cells. Terminal differentiation markers appeared only after induction of differentiation by specific protocols. The karyotype was stable, with few chromosomal changes, especially gains of chromosomes 5 and 20 and a chromosome 9p21 deletion resulting in p16 INK4A loss. A C228T TERT promoter mutation was present, but no other mutation typical of urothelial carcinoma. TP53 was wild-type and the cell cycle was arrested in response to genomic stress. Conclusions: HBLAK cells retain some differentiation potential and respond to cytotoxic agents similar to normal urothelial cells, but contain genetic changes contributing to immortalization in urothelial tumors. HBLAK may be valuable for evaluating the tumor specificity of novel cancer drugs, but may also be applied as an urothelial in vitro carcinogenesis model. |
| تدمد: | 2352-3735 2352-3727 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b10bb1d0fab244eb1a6e8e38acc910fcTest https://doi.org/10.3233/blc-160065Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b10bb1d0fab244eb1a6e8e38acc910fc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23523735 23523727 |
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