DIFFERENTIAL REGULATION OF CELL-CYCLE CHARACTERISTICS AND APOPTOSIS IN MMTV-MYC AND MMTV-RAS MOUSE MAMMARY-TUMORS

We have used the MMTV-myc and MMTV-ras transgenic mouse mammary tumor models (T. A. Stewart et al., Cell, 38: 627-637, 1984, and E. Sinn et al., Cell, 49: 465-475, 1987) to evaluate how the c-myc and v-Ha-ras o ncogenes influence tumor growth characteristics in vivo, MMTV-myc tumo rs had much higher levels of spontaneous apoptosis than MMTV-ras tumor s, whereas intermediate levels were observed in MMTV-myc/ras tumors, S ignificant differences in cell cycle characteristics were also observe d in tumors from mice of the three genotypes, Tumors from MMTV-myc mic e had lower G(1) and higher S-phase fractions than MMTV-ras tumors, wi th intermediate values again observed in the MMTV-myc/ras tumors, Desp ite these differences, however, tumor growth rates for the different g roups were similar, These findings highlight the importance of the bal ance between cell cycle regulation and cell death in determining the k inetics of tumor growth and indicate that distinct oncogenes can have a profound influence on that balance.