ELEVATED HIGH-MOBILITY GROUP-I(Y) GENE-EXPRESSION IS ASSOCIATED WITH PROGRESSIVE TRANSFORMATION OF MOUSE MAMMARY EPITHELIAL-CELLS

The high mobility group (HMG) proteins I and Y are well characterized nonhistone chromosomal proteins which bind to A . T-rich regions of DN A, and may regulate gene expression and/or DNA replication. We utilize d a series of mouse mammary epithelial preneoplastic and tumor cell li nes to explore the relationship between neoplastic transformation and HMG-I(Y) gene expression. The cell lines used in this study were origi nally derived from a single hyperplastic outgrowth, and exhibit a dist inct gradient of preneoplastic to highly metastatic transformation sta tes. We measured the levels of HMG-I(Y) gene expression in these cell lines during the different phases of cell growth in culture. At both s ubconfluent and confluent cell densities, elevated levels of HMG-I(Y) mRNA were directly correlated with the relative degree of neoplastic t ransformation and metastatic progression of these cells. HMG-I(Y) mRNA levels were always highest in proliferating cells. However. the diffe rences in HMG-I(Y) gene expression between the cell lines were greates t at confluent cell density, when the cells were not actively prolifer ating. HMG-I(Y) mRNA was detectable in normal primary mouse mammary ep ithelium proliferating in culture. However, the amount was much less t han that measured in the cell lines, indicating that elevated HMG-I(Y) gene expression was also directly correlated with the conversion of n ormal mammary epithelium to the preneoplastic immortalized state. Sout hern blot analysis showed that alterations in HMG-I(Y) loci are also a ssociated with the preneoplastic to neoplastic conversion of these cel l lines, and this change may involve a gene conversion event between t wo different HMG-I(Y) loci. These results indicate that there is a str ong correlation between elevated HMG-I(Y) gene expression and the prog ressive transformation of mouse mammary epithelial cells.