Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: Synergistic action of oncogenes in vivo

Cell cycle basis for the onset and progression of c-Myc-induced, TGFα-enhanced mouse mammary gland carcinogenesis

“…In addition, the tumors grow much faster than those occurring in the c-myc single transgenic strain (Amundadottir et al, 1995(Amundadottir et al, , 1996b). These data demonstrate that TGFa overexpression strikingly enhances c-Myc-induced carcinogenesis (Sinn et al, 1987), in line with the in vitro studies showing that cotransfection of cells with tgfa and c-myc e ectively induces transformed phenotype, in contrast to transfection of either gene alone (Amati et al, 1998;Land et al, 1983). The mechanisms for this synergistic in¯uence of TGFa are not yet fully clari®ed.…”

A transgenic mouse model for the ductal carcinoma in situ (DCIS) of the mammary gland

“…In the past several transgenic mouse lines have been established, using either the whey acidic protein promoter (Andres et al, 1987;Husler et al, 1998;Sandgren et al, 1995;Schoenenberger et al, 1988;Tzeng et al, 1993) or the mouse mammary tumor virus promoter (Choi et al, 1988;Daphna-Iken et al, 1998;Guy et al, 1992;Webster et al, 1995;Muller et al, 1988;Sinn et al, 1987) to target the expression of viral and cellular oncogenes to the mammary gland. Although in some cases identical or similar constructs were used to generate transgenic animals in di erent laboratories, the outcome with respect to mammary tumor incidence, latency of tumor formation, and tumor phenotype di ered signi®cantly between the obtained transgenic lines.…”

Signal transduction in mammary tumorigenesis: a transgenic perspective

“…Indeed, Ras mutations are found in many primary cancers, yet activating mutations are not considered to play a dramatic role in the etiology of breast carcinoma (Bos, 1989;Rochlitz et al, 1989). Mammary-speci®c expression of oncogenic vHa-ras in transgenic mice induces mammary carcinomas, arising as solitary tumors which are histologically distinct from the ErbB-2-induced comedo-carcinomas (Andres et al, 1987;Nielsen et al, 1991;Sinn et al, 1987). Until recently it has been di cult to assess tissue samples for Ras activation directly (Scheele et al, 1995), yet Ras e ector pathways are found activated in many breast cancers samples and derived cell lines, suggesting that Ras is activated in primary tumors.…”