Cancer Research AACR Conference on Molecular Diagnostics - 2008 Tumor Immunology: New Perspectives
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[Cancer Research 60, 4256-4261, August 1, 2000]
© 2000 American Association for Cancer Research

Tumor Biology

The Oncogenic Properties of the HMG-I Gene Family1

Lisa J. Wood, Joseph F. Maher2, Tracie E. Bunton3 and Linda M. S. Resar4

Hematology Division (L. J. W., L. M. S. R.) and Departments of Pediatrics (L. J. W., L. M. S. R.), Molecular Biology and Genetics (J. F. M.), Comparative Medicine (T. E. B.), and Oncology (L. M. S. R.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

The HMG-I gene family encodes high mobility group proteins originally identified as nonhistone chromosomal binding proteins. HMG-I and -Y proteins are alternatively spliced products of the same mRNA; HMG-C is encoded by a separate gene. The HMG-I proteins function as architectural chromatin-binding proteins that bind to the narrow groove of AT-rich regions in double-stranded DNA. Recent studies indicate an important role for HMG-I proteins in regulating gene expression. Moreover, increased expression of the HMG-I, -Y, and -C proteins correlates with cellular proliferation and neoplastic transformation in several cell types and human cancers. Previous work from our laboratory has shown that HMG-I is a direct c-Myc target gene that is involved in Myc-mediated neoplastic transformation. In this report, we show that increased expression of HMG-Y or -C leads to transformation with anchorage-independent cell growth in two experimental cell lines in a manner similar to that of HMG-I or c-Myc. Moreover, Rat 1a cells overexpressing HMG-Y or -C form tumors in nude mice analogous to Rat 1a cells overexpressing HMG-I or c-Myc. Distant metastases developed in animals injected with cells overexpressing HMG-I or -C. Our findings suggest that the HMG-I gene family is involved in neoplastic transformation and may represent a new family of oncogenes important in the pathogenesis of several human cancers.




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