The HMG-I Oncogene Causes Highly Penetrant, Aggressive Lymphoid Malignancy in Transgenic Mice and Is Overexpressed in Human Leukemia

HMG-I/Y is overexpressed in human cancer, although a direct role for this gene in transformation has not been established. We generated transgenic mice with HMG-I targeted to lymphoid cells. All seven informative founder HMG-I mice developed aggressive lymphoma by a mean age of 4.8 months. Tumors express T-cell markers and are transplantable. We also demonstrate that HMG-I mRNA and protein are increased in human acute lymphocytic leukemia samples. Our results show that HMG-I functions as an oncogene and suggest that it contributes to the pathogenesis of leukemia and other cancers with increased HMG-I expression.

[1]  G. Chiappetta,et al.  High-mobility group A1 proteins are overexpressed in human leukaemias. , 2003, The Biochemical journal.

[2]  N. Harris,et al.  Bethesda proposals for classification of lymphoid neoplasms in mice. , 2002, Blood.

[3]  L. Resar,et al.  HMG-I/Y in human breast cancer cell lines , 2002, Breast Cancer Research and Treatment.

[4]  W. Isaacs,et al.  High mobility group protein I(Y): a candidate architectural protein for chromosomal rearrangements in prostate cancer cells. , 2002, Cancer research.

[5]  T. Poggio,et al.  Prediction of central nervous system embryonal tumour outcome based on gene expression , 2002, Nature.

[6]  S. Lomvardas,et al.  Coordination of a transcriptional switch by HMGI(Y) acetylation. , 2001, Science.

[7]  R. Reeves,et al.  Architectural Transcription Factor HMGI(Y) Promotes Tumor Progression and Mesenchymal Transition of Human Epithelial Cells , 2001, Molecular and Cellular Biology.

[8]  L. Resar,et al.  HMG-I/Y, a New c-Myc Target Gene and Potential Oncogene , 2000, Molecular and Cellular Biology.

[9]  L. Resar,et al.  The oncogenic properties of the HMG-I gene family. , 2000, Cancer research.

[10]  G. Chiappetta,et al.  Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasias. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[11]  H. Dintzis,et al.  Malignant transformation of early lymphoid progenitors in mice expressing an activated Blk tyrosine kinase. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[12]  U. K. Laemmli,et al.  SARs are cis DNA elements of chromosome dynamics: Synthesis of a SAR repressor protein , 1995, Cell.

[13]  U. K. Laemmli,et al.  Metaphase chromosome structure: Bands arise from a differential folding path of the highly AT-rich scaffold , 1994, Cell.

[14]  T. Maniatis,et al.  Mechanisms of transcriptional synergism between distinct virus-inducible enhancer elements , 1993, Cell.

[15]  M. Davisson,et al.  Chromosomal localization of the murine gene and two related sequences encoding high-mobility-group I and Y proteins. , 1992, Genomics.

[16]  H. Pircher,et al.  T cell tolerance to Mlsa encoded antigens in T cell receptor V beta 8.1 chain transgenic mice. , 1989, The EMBO journal.

[17]  P. Leder,et al.  Transgenic mice bearing the human c-myc gene activated by an immunoglobulin enhancer: a pre-B-cell lymphoma model. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[18]  R. Palmiter,et al.  The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice , 1985, Nature.

[19]  S. Laland,et al.  On the presence of two new high mobility group‐like proteins in HeLa S3 cells , 1983, FEBS letters.