Wild-type K-ras has a tumour suppressor effect on carcinogen-induced murine colorectal adenoma formation

International Journal of Experimental Pathology
Feijun LuoM J Arends

Abstract

K-ras mutations are found in ~40% of human colorectal adenomas and carcinomas and contribute to colorectal tumour formation at an early stage. Wild-type K-ras has been reported to be deleted in some tumours, but the consequences of changes in wild-type K-ras copy number for experimental colorectal carcinogenesis have not been investigated. To characterize the effects of K-ras copy number changes on formation of carcinogen-induced colorectal neoplasms in mice, wild-type (K-ras(+/+) ) and heterozygous K-ras exon 1 knockout (K-ras(+/-) ) mice were given 10 weekly treatments of 1, 2-dimethylhydrazine (DMH) to induce colorectal tumours. Colorectal expression levels of K-ras 4A and 4B transcripts in K-ras(+/-) mice were ~50% decreased compared with K-ras(+/+) mice. One year after DMH treatment, survival of K-ras(+/-) mice decreased from 88 to 82% compared with wild-type mice. Colorectal adenomas significantly increased from 0.52 ± 0.15 in K-ras(+/+) mice to 0.87 ± 0.14 in K-ras(+/-) mice (mean ± SEM per mouse, P < 0.01); total tumour volume increased 2.13-fold (P < 0.05). Comparing K-ras(+/+) with K-ras(+/-) murine adenomas, Ki-67-positive proliferating tumour cells significantly increased from 7.77 ± 0.64% to 9.15 ± 0.92% and cleave...Continue Reading

References

Mar 1, 1991·Trends in Genetics : TIG·C J Marshall
Dec 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·I GuerreroA Pellicer
Jan 1, 1997·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·G SourvinosD A Spandidos
Nov 14, 1997·British Journal of Haematology·A Baccichet, D Sinnett
Oct 21, 1998·Oncogene·S L CampbellC J Der
Mar 21, 2000·Seminars in Immunology·M F Olson, R Marais
Sep 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·M ClassonE Harlow
Aug 31, 2001·Nature Genetics·Z ZhangM You
Jun 5, 2003·Nature Reviews. Cancer·Marcos Malumbres, Mariano Barbacid
Sep 24, 2004·International Journal of Cancer. Journal International Du Cancer·Roberto DiazAngel Pellicer
Oct 19, 2004·Oncogene·Douglas X MasonAthena W Lin
Jan 29, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Arvind SinghGayatri Ramakrishna
Dec 8, 2007·Experimental Cell Research·Charles E PatekMartin L Hooper
Feb 9, 2008·Gene Expression·Feijun LuoMark J Arends
Sep 23, 2010·Advances in Clinical Chemistry·Ben MarkmanJosep Tabernero

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Citations

Jun 16, 2014·Nature Chemical Biology·Jochen SpiegelHerbert Waldmann
Mar 22, 2015·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Martha Rocío Moreno-JimenezMinerva Ramos-Gomez
Jul 11, 2020·Cancer Metastasis Reviews·Tamás TakácsVirag Vas
Nov 26, 2021·Metabolomics : Official Journal of the Metabolomic Society·Dorna VarshaviJeremy R Everett

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