METASTASIS OF MAMMARY CARCINOMAS IN GRS A HYBRID MICE TRANSGENIC FOR THE MTS1 GENE/

Transgenic mice, carrying the mts1 gene, one of the genes involved in the acquisition of the metastatic phenotype, were generated, The mts1 gene was placed under the control of the mouse mammary tumor virus (MM TV) long terminal repeat (LTR) promoter leading to overexpression in t he lactating mammary gland of transgenic animals, Animals bearing the transgene appear phenotypically normal, Animals of two transgenic line s (Tg463 and Tg507) were crossed with the GRS/A mice, The GRS/A strain is characterized by high incidence of mammary tumors which rarely met astasize, 40% of the tumor bearing hybrid GRS/A mts1 females mere foun d to develop secondary tumors in the lungs, The Mts1 protein was detec ted in the transgene primary tumor cells as well as in the correspondi ng metastases, Nontransgenic littermates expressed the Mts1 protein on ly in the stromal cells surrounding the tumor but not in the tumor cel ls by itself, Taken together these observations indicate that overexpr ession of the mts1 gene in the mouse mammary carcinoma cells gives ris e to more aggressive tumors which are able to metastasize.