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Publication : An inbred colony of oncogene transgenic mice: diversity of tumours and potential as a therapeutic model.

First Author  Thomas H Year  1996
Journal  Br J Cancer Volume  73
Issue  1 Pages  65-72
PubMed ID  8554986 Mgi Jnum  J:72367
Mgi Id  MGI:2152513 Doi  10.1038/bjc.1996.12
Citation  Thomas H, et al. (1996) An inbred colony of oncogene transgenic mice: diversity of tumours and potential as a therapeutic model. Br J Cancer 73(1):65-72
abstractText  Transgenic mice carrying the activated rat c-neu oncogene under transcriptional control of the MMTV promoter were backcrossed to BALB/c mice, with the aim of developing a model for cancer therapy. A total of 86 of 268 transgene-positive mice in the first five generations developed 93 histologically diverse tumours (median age of onset 18 months). The cumulative incidence of breast tumours at 24 months was 18%, and overall tumour incidence 31%. As well as expected c-neu expressing breast cancers, lymphomas and Harderian gland carcinomas developed. Virgin mice had fewer mammary tumours than those with two litters. Breast carcinomas metastasised to the lungs, and lymphomas were widely disseminated. The tumours showed a range of architectural patterns, which resembled human breast cancers or lymphomas. This diversity was reflected in S-phase fraction and aneuploidy. Breast tumours transplanted to nude mice showed variable responses to interferon (IFN)-alpha and gamma. A tumour transplanted to BALB/c mice responded to interleukin (IL)-12. There was significant decline in transgene positivity with successive generations. The diversity, histological and biological resemblance to human cancer suggests that the model has potential for evaluating novel therapies. However, further genetic and environmental manipulations are required to increase tumour incidence and decrease age of onset.
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