The mammary tumor system has been useful both in the identification and characterization of genes involved in the development and transformation of mammary epithelium. Further characterization of the Notch related Int-3 gene reveals that it encodes a 6.2kb message expressed at a low level in almost all adult tissues and appears to be transcriptionally active as early as day 8 n developing embryos. We have demonstrated in the """"""""normal"""""""" HC11 mouse mammary cell line that the activated Int-3 gene transforms these cells to anchorage independence while maintaining the normal growth kinetics suggesting a mode of transformation though direct cell-cell interactions. This is in contrast to what we had previously observed with /nt-2 transformed HC-11 cells. In addition, expression of activated Int-3 abrogates the ability of HC11 cells to express beta-caesin in response to lactogenic hormones. The HC11 cells, while maintaining certain characteristics of normal cells, are immortal. Further analysis of this cell line reveals that one allele of the Trp53 gene contains a microdeletion of seven codons in exon 5 and the other allele contains a missense mutation in exon 6. Analysis of one of the MMTV induced mammary hyperplastic outgrowth (HOG) lines in CZECHIl mice has led to the identification of a new common insertion site for MMTV. We have named this new site /nt-6. It was found to rearranged by MMTV , four independent tumors. Preliminary data indicated that the gene encodes a 1.4 kb RNA transcript and is located on chromosome 15 in the mouse. Each of the endogenous superantigens analyzed to date is determined by one or more MMTV proviral genomes. To assess the ability of self ligands other than MMTV to mediate the deletion of specific populations of T-cells during T- cell development, the T-cell receptor beta chain (Tcrb-V) repertoire was characterized in CZECH Il mice. These mice lack endogenous MMTV proviral genomes. Our results showed that although CZECHII mice express some Tcrb-V products at frequencies lower than those observed in nondeleting conventional mouse strains, these instances do not however appear to involve negative selection. These results are consistent with the conclusion that endogenous superantigens are uniquely the products of integrate proviral genomes.
