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Epithelial Carcinogenesis in the Mouse: Correlating the Genetics and the Biology

Sheelagh Frame, Robbie Crombie, Jennie Liddell, Debbie Stuart, Spiros Linardopoulos, Hiroki Nagase, Giuseppe Portella, Ken Brown, Alasdair Street, Rosemary Akhurst and Allan Balmain
Philosophical Transactions: Biological Sciences
Vol. 353, No. 1370, Epithelial Cell Growth and Differentiation (Jun. 29, 1998), pp. 839-845
Published by: Royal Society
Stable URL: http://www.jstor.org/stable/56742
Page Count: 7
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Epithelial Carcinogenesis in the Mouse: Correlating the Genetics and the Biology
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Abstract

Tumour formation relies on a complex combination of genetic and environmental factors. In particular, the contributions from inherited predisposition genes as well as carcinogens, for example from cigarettes or in the diet, are amongst the major contributors to tumorigenesis. Since the study of such processes is particularly difficult in human cancers, the availability of a well-defined model system is of obvious benefit. The mouse skin model of multistage carcinogenesis offers an excellent tool for the study of the target cells, the target genes and the biological events associated with neoplasia. In this system, tumorigenesis occurs in a series of defined stages, each of which is characterized by specific and reproducible alterations in genes such as H-ras, cyclin D1, p53 and p16INK4A. Additional changes occur in the production of, or response to, factors such as transforming growth factor β (TGFβ ). These genetic and biological alterations are mirrored in human tumours of epithelial origin. Hence, research into the general principles of tumour initiation, promotion and progression in the context of the mouse skin model is likely to prove valuable in the continual search for new methods for the diagnosis, prevention, and therapeutic treatment of human cancers.

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