The oncogenic properties of the HMG-I gene family

• Published in: Cancer research (Chicago, Ill.) Vol. 60; no. 15; pp. 4256 - 4261
• Main Authors: Wood, L J, Maher, J F, Bunton, T E, Resar, L M
• Format: Journal Article
• Language: English
• Published: United States 01.08.2000
• Subjects: Animals; c-Myc protein; Cell Adhesion - physiology; Cell Line; Cell Transformation, Neoplastic - genetics; Gene Expression; high mobility group protein C; high mobility group protein Y; High Mobility Group Proteins - biosynthesis; High Mobility Group Proteins - genetics; High Mobility Group Proteins - physiology; HMG-I gene; HMGA1a Protein; Humans; Mice; Mice, Nude; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Oncogenes - physiology; Rats; Transcription Factors - biosynthesis; Transcription Factors - genetics; Transcription Factors - physiology; Transfection
• ISSN: 0008-5472

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 la 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.