Epithelial carcinogenesis in the mouse: correlating the genetics and the biology.
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 in 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 beta (TGF beta). 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.
Frame
S
S
CRC Beatson Laboratories, Department of Medical Oncology, Glasgow, UK.
Crombie
R
R
Liddell
J
J
Stuart
D
D
Linardopoulos
S
S
Nagase
H
H
Portella
G
G
Brown
K
K
Street
A
A
Akhurst
R
R
Balmain
A
A
D000818:Animals; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic; D019938:Cyclin D1 / Q000235:genetics; D004249:DNA Damage; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology*; D019942:Genes, p16; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
D019938:Cyclin D1