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 Hensen, K. Articles by Voz, M. L. Search for Related Content PubMed PubMed Citation Articles by Hensen, K. Articles by Voz, M. L.

The Tumorigenic Diversity of the Three PLAG Family Members Is Associated with Different DNA Binding Capacities¹

Laboratory for Molecular Oncology, Center for Human Genetics (CME), University of Leuven (KUL) and Flanders Interuniversity Institute for Biotechnology (VIB), Herestraat 49 B-3000 Leuven, Belgium

Pleomorphic adenoma gene (PLAG) 1, the main translocation target in pleomorphic adenomas of the salivary glands, is a member of a new subfamily of zinc finger proteins comprising the tumor suppressor candidate PLAG-like1 (also called ZAC1 or lost on transformation 1) and PLAGL2. In this report, we show that NIH3T3 cells overexpressing PLAG1 or PLAGL2 display the typical markers of neoplastic transformation: (a) the cells lose cell-cell contact inhibition; (b) show anchorage-independent growth; and (c) are able to induce tumors in nude mice. In contrast, PLAGL1 has been shown to prevent the proliferation of tumor cells by inducing cell cycle arrest and apoptosis. This difference in function is also reflected in their DNA binding, as we show here that the three PLAG proteins, although highly homologous in their DNA-binding domain, bind different DNA sequences in a distinct fashion. Interestingly, the PLAG1- and PLAGL2-induced transformation is accompanied by a drastic up-regulation of insulin-like growth factor-II, which we prove is a target of PLAG1 and PLAGL2. This strongly suggests that the oncogenic capacity of PLAG1 and PLAGL2 is mediated at least partly by activating the insulin-like growth factor-II mitogenic pathway.

This article has been cited by other articles:

				Y.-S. Yang, M.-C. W. Yang, Y. Guo, O. W. Williams, and J. C. Weissler PLAGL2 expression-induced lung epithelium damages at bronchiolar alveolar duct junction in emphysema: bNip3- and SP-C-associated cell death/injury activity Am J Physiol Lung Cell Mol Physiol, September 1, 2009; 297(3): L455 - L466. [Abstract] [Full Text] [PDF]

				M. C. B. Ammons, D. W. Siemsen, L. K. Nelson-Overton, M. T. Quinn, and K. A. Gauss Binding of Pleomorphic Adenoma Gene-like 2 to the Tumor Necrosis Factor (TNF)-{alpha}-responsive Region of the NCF2 Promoter Regulates p67phox Expression and NADPH Oxidase Activity J. Biol. Chem., June 15, 2007; 282(24): 17941 - 17952. [Abstract] [Full Text] [PDF]

				G. Zheng and Y.-C. Yang Sumoylation and Acetylation Play Opposite Roles in the Transactivation of PLAG1 and PLAGL2 J. Biol. Chem., December 9, 2005; 280(49): 40773 - 40781. [Abstract] [Full Text] [PDF]

				Y. Lu, P.-Y. Liu, P. Xiao, and H.-W. Deng Hotelling's T2 multivariate profiling for detecting differential expression in microarrays Bioinformatics, July 15, 2005; 21(14): 3105 - 3113. [Abstract] [Full Text] [PDF]

				J. Declercq, F. Van Dyck, C. V. Braem, I. C. Van Valckenborgh, M. Voz, M. Wassef, L. Schoonjans, B. Van Damme, L. Fiette, and W. J.M. Van de Ven Salivary Gland Tumors in Transgenic Mice with Targeted PLAG1 Proto-Oncogene Overexpression Cancer Res., June 1, 2005; 65(11): 4544 - 4553. [Abstract] [Full Text] [PDF]

				S. F. Landrette, Y.-H. Kuo, K. Hensen, S. B. van Waalwijk van Doorn-Khosrovani, P. N. Perrat, W. J. M. Van de Ven, R. Delwel, and L. H. Castilla Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11 Blood, April 1, 2005; 105(7): 2900 - 2907. [Abstract] [Full Text] [PDF]

				M.-C. W. Yang, J. C. Weissler, L. S. Terada, F. Deng, and Y.-S. Yang Pleiomorphic Adenoma Gene-Like-2, a Zinc Finger Protein, Transactivates the Surfactant Protein-C Promoter Am. J. Respir. Cell Mol. Biol., January 1, 2005; 32(1): 35 - 43. [Abstract] [Full Text] [PDF]

				F. Van Dyck, E. L. D. Delvaux, W. J. M. Van de Ven, and M. V. Chavez Repression of the Transactivating Capacity of the Oncoprotein PLAG1 by SUMOylation J. Biol. Chem., August 20, 2004; 279(34): 36121 - 36131. [Abstract] [Full Text] [PDF]

				L. H. Castilla, P. Perrat, N. J. Martinez, S. F. Landrette, R. Keys, S. Oikemus, J. Flanegan, S. Heilman, L. Garrett, A. Dutra, et al. Identification of genes that synergize with Cbfb-MYH11 in the pathogenesis of acute myeloid leukemia PNAS, April 6, 2004; 101(14): 4924 - 4929. [Abstract] [Full Text] [PDF]