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 Zaidi, M. R. Articles by Chada, K. K. Search for Related Content PubMed PubMed Citation Articles by Zaidi, M. R. Articles by Chada, K. K.

Misexpression of Full-length HMGA2 Induces Benign Mesenchymal Tumors in Mice

¹ Graduate School of Biomedical Sciences and ² Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey; and ³ Department of Pathology, Keio University School of Medicine, Tokyo, Japan

Requests for reprints: Kiran K. Chada, Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854. E-mail: chada{at}umdnj.edu.

The high-mobility group AT-hook 2 (HMGA2) protein is a member of the high-mobility group family of the DNA-binding architectural factors and participates in the conformational regulation of active chromatin on its specific downstream target genes. HMGA2 is expressed in the undifferentiated mesenchyme and is undetectable in their differentiated counterparts, suggesting its functional importance in mesenchymal cellular proliferation and differentiation. Interestingly, it is a frequent target of chromosomal translocations in several types of human benign differentiated mesenchymal tumors, including lipomas, fibroadenomas of the breast, salivary gland adenomas, and endometrial polyps. The translocations lead to a variety of HMGA2 transcripts, which range from wild-type, truncated, and fusion mRNA species. However, it is not clear whether alteration of the HMGA2 transcript is required for its tumorigenic potential. To determine whether misexpression of HMGA2 in differentiated mesenchymal cells is sufficient to cause tumorigenesis, we produced transgenic mice that misexpressed full-length or truncated human HMGA2 transcript under the control of the differentiated mesenchymal cell (adipocyte)–specific promoter of the adipocyte P2 (Fabp4) gene. Expression of the full-length HMGA2 transgene was observed in a number of tissues, which produced neoplastic phenotype, including fibroadenomas of the breast and salivary gland adenomas. Furthermore, transgenic misexpression of the truncated version of HMGA2, containing only the three DNA-binding domains, produced similar phenotypes. These results show that misexpression of HMGA2 in a differentiated mesenchymal cell is sufficient to cause mesenchymal tumorigenesis and is independent of the nature of the HMGA2 transcript that results from chromosomal translocations observed in humans. (Cancer Res 2006; 66(15): 7453-9)

This article has been cited by other articles:

				F. Di Cello, J. Hillion, A. Hristov, L. J. Wood, M. Mukherjee, A. Schuldenfrei, J. Kowalski, R. Bhattacharya, R. Ashfaq, and L. M.S. Resar HMGA2 Participates in Transformation in Human Lung Cancer Mol. Cancer Res., May 1, 2008; 6(5): 743 - 750. [Abstract] [Full Text] [PDF]

				K. Motoyama, H. Inoue, Y. Nakamura, H. Uetake, K. Sugihara, and M. Mori Clinical Significance of High Mobility Group A2 in Human Gastric Cancer and Its Relationship to let-7 MicroRNA Family Clin. Cancer Res., April 15, 2008; 14(8): 2334 - 2340. [Abstract] [Full Text] [PDF]

				S. A. Pangas, X. Li, L. Umans, A. Zwijsen, D. Huylebroeck, C. Gutierrez, D. Wang, J. F. Martin, S. P. Jamin, R. R. Behringer, et al. Conditional Deletion of Smad1 and Smad5 in Somatic Cells of Male and Female Gonads Leads to Metastatic Tumor Development in Mice Mol. Cell. Biol., January 1, 2008; 28(1): 248 - 257. [Abstract] [Full Text] [PDF]

				A. R.J. Young and M. Narita Oncogenic HMGA2: short or small? Genes & Dev., May 1, 2007; 21(9): 1005 - 1009. [Full Text] [PDF]

				Y. S. Lee and A. Dutta The tumor suppressor microRNA let-7 represses the HMGA2 oncogene Genes & Dev., May 1, 2007; 21(9): 1025 - 1030. [Abstract] [Full Text] [PDF]

				G. Cattaruzzi, S. Altamura, M. A. Tessari, A. Rustighi, V. Giancotti, C. Pucillo, and G. Manfioletti The second AT-hook of the architectural transcription factor HMGA2 is determinant for nuclear localization and function Nucleic Acids Res., March 19, 2007; 35(6): 1751 - 1760. [Abstract] [Full Text] [PDF]