IDENTIFICATION OF INBRED MOUSE STRAINS HARBORING GENETIC MODIFIERS OFMAMMARY-TUMOR AGE-OF-ONSET AND METASTATIC PROGRESSION

Metastasis is one of the most important and complex processes in human neoplastic disease. A large number of both positive and negative even ts must occur to permit a tumor cell to colonize a distant site succes sfully. To identify mouse strains that harbor dominant genetic modifie rs of this process, a strain survey was initiated utilizing a transgen ic mouse mammary tumor model that exhibits a high incidence of pulmona ry metastases. The transgenic animal was bred to 27 different inbred s trains of mice and scored for the metastatic organ tropism and metasta tic density. Thirteen strains were identified that had a statistically significant reduction in the numbers of pulmonary metastases. In addi tion, 10 strains were identified that altered the kinetics of inductio n of the primary mammary tumor. These strains will likely provide usef ul model systems for the analysis of genetic interactions in the initi ation and progression of mammary adenocarcinomas. Int. J. Cancer 77:64 0-644, 1998. (C) 1998 Wiley-Liss, Inc.