THE RAT GENE HOMOLOGOUS TO THE HUMAN GENE-9-27 IS INVOLVED IN THE DEVELOPMENT OF THE MAMMARY-GLAND

We have developed a model system for studying differentiation in the m ammary gland, by using two clonal cultures deriving from a rat breast adenocarcinoma, They differ in the ability to form domes, structures t he significance of which is unknown. By using the subtractive cDNA lib rary approach, we isolated a cDNA that is highly expressed in the dome -forming cells, and identical to the rats gene and highly homologous t o the human 9-27 gene, Antisense treatment of the dome-forming cells s pecifically and reproducibly abolishes dome formation, while forced ex pression of the gene in non-dome-forming cells causes morphological ch anges suggestive of ''flat'' domes, In situ hybridization on rat tissu es shows that the gene is expressed in epithelia, especially in those forming tubular structures, suggesting a relatedness between these str uctures and domes, Cytokeratin 8 and E cadherin are strongly expressed in the domes but not outside them, suggesting that the rats gene trig gers the cells to express molecules that tighten the lateral connectio ns between the cells; the process is likely to parallel that occurring during the differentiation of the mammary gland.