The oncogenic properties of the HMG-I gene family

The HMG-I gene family encodes high mobility group proteins originally ident ified as nonhistone chromosomal binding proteins. HMG-I and -Y proteins are alternatively spliced products of the same mRNA; HMG-C is encoded by a sep arate gene. The HMG-I proteins function as architectural chromatin-binding proteins that bind to the narrow groove of AT-rich regions in double-strand ed DNA, Recent studies indicate an important role for HMG-I proteins in reg ulating gene expression. Moreover, increased expression of the HMG-I, -Y, a nd -C proteins correlates with cellular proliferation and neoplastic transf ormation in several cell types and human cancers. Previous work from our la boratory has shown that HMG-I is a direct c-Myc target gene that is involve d in Myc-mediated neoplastic transformation. In this report, we show that i ncreased expression of HMG-Y or -C leads to transformation with anchorage-i ndependent cell growth in two experimental cell lines in a manner similar t o that of HMG-I or c-Myc, Moreover, Rat la cells overexpressing HMG-Y or -C form tumors in nude mice analogous to Rat la cells overexpressing HMG-I or c-Myc, Distant metastases developed in animals injected with cells overexp ressing HMG-I or -C. Our findings suggest that the HMG-I gene family is inv olved in neoplastic transformation and may represent a new family of oncoge nes important in the pathogenesis of several human cancers.