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- W1673520565 abstract "3856 Mouse tumor models with spontaneously developing sporadic tumors are important to cancer research to generate new hypotheses in tumor biology and to test new treatment strategies. Ideally tumor induction should mimic natural tumor development and lead to a small number of molecularly well defined tumors. Most Cre recombinase inducible tumor models show a marked field cancerization as most if not all target cells express the oncogen after induction. We have used the transgenic mouse strain RasF (Meuwissen et. al., Oncogene 2001) expressing a Cre recombinase inducible Ras oncogene. In these mice the number of tumors that develop can be influenced by the dose of recombinant Adneo virally encoded CRE that is given. However, a large number of Lung adenocarcinomas develop in both lungs and a strong anti-viral immune response is induced. To generate a mouse tumor model that more closely resembles the human pathogenesis without the use of Adenoviral vectors, we have used recombinant Cre recombinase fused to the basic membrane translocation peptide TAT (TAT-Cre). Injection of TAT-Cre recombinant protein into one lung of immunocompetent RasF mice yields a small number of pulmonary adenocarcinomas after a short latency in the injected lung without the need for immunsuppression. Since only a limited number of tumors developed in these mice, respiratory distress due to a large tumor burden was greatly reduced and the animals survived for a longer period of time compared to an Adenoviral Cre delivery system. The TAT-Cre protein was not immunstimulatory as pulmonary dendritic cells did not upregulate CD40 or CD86 after TAT-Cre application. In summary, we present a novel approach to reliably deliver Cre recombinase in vivo to induce a limited number of sporadic orthotopic tumors in mice. The protocol has no need for immune suppression and mimicks human cancer formation with a prolonged observatory window to test new therapeutic approaches." @default.
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- W1673520565 date "2007-05-01" @default.
- W1673520565 modified "2023-09-27" @default.
- W1673520565 title "In vivo use of recombinant TAT-CRE protein for sporadic lung cancer induction in a orthotopic mouse tumor model." @default.
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