Abstract
We have analysed the pattern of β-catenin expression by immunohistochemistry in mice singly or multiply mutant for Apc, p53 and Msh2. We observed increased expression of β-catenin in all intestinal lesions arising on an ApcMin+/− background. In all categories of lesion studied mosaic patterns of β-catenin expression were observed, with the proportion of cells showing enhanced expression decreasing with increasing lesion size. p53 status did not alter these patterns. We also show that β-catenin dysregulation marks pancreatic abnormalities occurring in ApcMin+/− and (ApcMin+/−, p53−/−) mice. In these mice both adenomas and adenocarcinomas of the pancreas arose and were characterized by increased expression of β-catenin. We have extended these analyses to intestinal lesions arising in mice mutant for the mismatch repair gene Msh2. In these mice, increased expression of β-catenin was again observed. However, in contrast with ApcMin+/− mice, a subset of lesions retained normal expression. Taken together, these findings show that increased expression of β-catenin is an efficient marker of early neoplastic change in both murine intestine and pancreas in Apc mutant mice. However, we also show that dysregulation of β-catenin is not an obligate step in the development of intestinal lesions, and therefore that genetic events other than the loss of Apc function may initiate the transition from normal to neoplastic epithelium.
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Acknowledgements
We wish to thank Hein te Riele for supply of Msh-2 deficient mice, James Going for assistance with microdissection and John Verth and his staff for animal maintenance. AR Clarke is a Royal Society University Research Fellow. This work was supported by SHERT, the Cancer Research Campaign and by a grant from the government of Thailand to R Kongkanuntn.
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Kongkanuntn, R., Bubb, V., Sansom, O. et al. Dysregulated expression of β-catenin marks early neoplastic change in Apc mutant mice, but not all lesions arising in Msh2 deficient mice. Oncogene 18, 7219–7225 (1999). https://doi.org/10.1038/sj.onc.1203181
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DOI: https://doi.org/10.1038/sj.onc.1203181
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