The simultaneous induction of tumorigenesis and Cre-loxP recombination in mice.

To investigate the role of Rac1 for tumorigenesis, we generated inducible transgenic (Tg) mice that simultaneously express polyomavirus middle T antigen (mT) and Cre recombinase under the control of mouse mammary tumor virus long terminal repeat (MMTV-LTR) promoter (MMTV-LTR-tTA/mT-TRE-cre Tg). MMTV-LTR-tTA/mT- TRE-cre Tg mice formed tumors in the subcutaneous tissue and developed lung metastasis. We examined tumor latency and types in rac1 deficient (rac1(flox/-)) and control (rac1(+/+), rac1(+/-) or rac1(flox/+)) MMTV-LTR-tTA/mT-TRE-cre Tg mice and found that formation of cutaneous appendage tumor was suppressed although tumor latency in these mice was not affected by loss of Rac1. These results suggested that Rac1 may play a pivotal role in induction and growth of the mT-mediated epithelial tumors. MMTV-LTR-tTA/mT-TRE-cre Tg mice would provide a versatile animal model to investigate genetic interaction in the tumorigenesis.