This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Struckmann, K. Articles by Moch, H. Search for Related Content PubMed PubMed Citation Articles by Struckmann, K. Articles by Moch, H.

Impaired Expression of the Cell Cycle Regulator BTG2 Is Common in Clear Cell Renal Cell Carcinoma

Institute for Pathology, University of Basel, Basel, Switzerland

The prognosis of patients with renal cell carcinoma (RCC) is poor. A full understanding of the molecular genetics and signaling pathways involved in renal cancer development and in the metastatic process is of central importance for developing innovative and novel treatment options. In this study, BD Atlas Human Cancer 1.2 cDNA microarrays were used to identify genes involved in renal tumorigenesis. By analyzing gene expression patterns of four clear cell RCC (cRCC) cell lines and normal renal tissue, 25 genes were found differentially expressed. To determine the relevance of these genes, RNA in situ hybridization was performed on a tissue microarray generated from 61 snap-frozen primary renal cell carcinomas and 12 normal renal cortex biopsies. B-cell translocation gene 2 (BTG2), a negative cell cycle regulator, which was expressed in normal renal tissue but down-regulated in cRCC cell lines and primary cRCCs, was selected for additional experiments. Quantitative BTG2 mRNA expression analysis in 42 primary cRCCs and 18 normal renal cortex biopsies revealed up to 44-fold reduced expression in the tumor tissues. Decrease of BTG2 expression was not associated with tumor stage, grade, and survival. Cell culture experiments demonstrated that BTG2 expression was weakly inducible by the phorbolester 12-O-tetradecanoylphorbol-13-acetate in one of four cRCC cell lines. In contrast, increasing cell density led to elevated BTG2 mRNA expression in three of four cRCC cell lines. In both experiments, BTG2 mRNA levels did not reach values observed in normal renal tissue. These data suggest that down-regulation of BTG2 is an important step in renal cancer development.

This article has been cited by other articles:

				Y.-B. Lim, T. J. Park, and I. K. Lim B Cell Translocation Gene 2 Enhances Susceptibility of HeLa Cells to Doxorubicin-induced Oxidative Damage J. Biol. Chem., November 28, 2008; 283(48): 33110 - 33118. [Abstract] [Full Text] [PDF]

				R. J. Wozniak, S. Keles, J. J. Lugus, K. H. Young, M. E. Boyer, T. M. Tran, K. Choi, and E. H. Bresnick Molecular Hallmarks of Endogenous Chromatin Complexes Containing Master Regulators of Hematopoiesis Mol. Cell. Biol., November 1, 2008; 28(21): 6681 - 6694. [Abstract] [Full Text] [PDF]

				M. R.H. Estecio, P. S. Yan, A. E.K. Ibrahim, C. S. Tellez, L. Shen, T. H.-M. Huang, and J.-P. J. Issa High-throughput methylation profiling by MCA coupled to CpG island microarray Genome Res., October 1, 2007; 17(10): 1529 - 1536. [Abstract] [Full Text] [PDF]

				S. Farioli-Vecchioli, M. Tanori, L. Micheli, M. Mancuso, L. Leonardi, A. Saran, M. T. Ciotti, E. Ferretti, A. Gulino, S. Pazzaglia, et al. Inhibition of medulloblastoma tumorigenesis by the antiproliferative and pro-differentiative gene PC3 FASEB J, July 1, 2007; 21(9): 2215 - 2225. [Abstract] [Full Text] [PDF]

				L. J. Donato, J. H. Suh, and N. Noy Suppression of Mammary Carcinoma Cell Growth by Retinoic Acid: the Cell Cycle Control Gene Btg2 Is a Direct Target for Retinoic Acid Receptor Signaling Cancer Res., January 15, 2007; 67(2): 609 - 615. [Abstract] [Full Text] [PDF]

				H. Was, T. Cichon, R. Smolarczyk, D. Rudnicka, M. Stopa, C. Chevalier, J. J. Leger, B. Lackowska, A. Grochot, K. Bojkowska, et al. Overexpression of Heme Oxygenase-1 in Murine Melanoma: Increased Proliferation and Viability of Tumor Cells, Decreased Survival of Mice Am. J. Pathol., December 1, 2006; 169(6): 2181 - 2198. [Abstract] [Full Text] [PDF]

				V. Busygina, M. C. Kottemann, K. L. Scott, S. E. Plon, and A. E. Bale Multiple Endocrine Neoplasia Type 1 Interacts with Forkhead Transcription Factor CHES1 in DNA Damage Response. Cancer Res., September 1, 2006; 66(17): 8397 - 8403. [Abstract] [Full Text] [PDF]

				D. Passeri, A. Marcucci, G. Rizzo, M. Billi, M. Panigada, L. Leonardi, F. Tirone, and F. Grignani Btg2 enhances retinoic Acid-induced differentiation by modulating histone h4 methylation and acetylation. Mol. Cell. Biol., July 1, 2006; 26(13): 5023 - 5032. [Abstract] [Full Text] [PDF]

				F. Lopez-Rios, S. Chuai, R. Flores, S. Shimizu, T. Ohno, K. Wakahara, P. B. Illei, S. Hussain, L. Krug, M. F. Zakowski, et al. Global Gene Expression Profiling of Pleural Mesotheliomas: Overexpression of Aurora Kinases and P16/CDKN2A Deletion as Prognostic Factors and Critical Evaluation of Microarray-Based Prognostic Prediction. Cancer Res., March 15, 2006; 66(6): 2970 - 2979. [Abstract] [Full Text] [PDF]

				A. D. Boiko, S. Porteous, O. V. Razorenova, V. I. Krivokrysenko, B. R. Williams, and A. V. Gudkov A systematic search for downstream mediators of tumor suppressor function of p53 reveals a major role of BTG2 in suppression of Ras-induced transformation Genes & Dev., January 15, 2006; 20(2): 236 - 252. [Abstract] [Full Text] [PDF]

				J. W. Hong, M. S. Ryu, and I. K. Lim Phosphorylation of Serine 147 of tis21/BTG2/pc3 by p-Erk1/2 Induces Pin-1 Binding in Cytoplasm and Cell Death J. Biol. Chem., June 3, 2005; 280(22): 21256 - 21263. [Abstract] [Full Text] [PDF]

				Y. Li, X. Hong, M. Hussain, S. H. Sarkar, R. Li, and F. H. Sarkar Gene expression profiling revealed novel molecular targets of docetaxel and estramustine combination treatment in prostate cancer cells Mol. Cancer Ther., March 1, 2005; 4(3): 389 - 398. [Abstract] [Full Text] [PDF]

				S. Park, Y. J. Lee, H.-J. Lee, T. Seki, K.-H. Hong, J. Park, H. Beppu, I. K. Lim, J.-W. Yoon, E. Li, et al. B-Cell Translocation Gene 2 (Btg2) Regulates Vertebral Patterning by Modulating Bone Morphogenetic Protein/Smad Signaling Mol. Cell. Biol., December 1, 2004; 24(23): 10256 - 10262. [Abstract] [Full Text] [PDF]

				M.-H. Tan, C. G. Rogers, J. T. Cooper, J. A. Ditlev, T. J. Maatman, X. Yang, K. A. Furge, and B. T. Teh Gene Expression Profiling of Renal Cell Carcinoma Clin. Cancer Res., September 15, 2004; 10(18): 6315S - 6321S. [Abstract] [Full Text] [PDF]