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• W2086177514 abstract "Abstract Colorectal cancer arises after a series of mutational events in the colon epithelia and is often used as a model of the multistep progression of tumorigenesis. Mutations in Ki‐Ras have been detected in some 50% of cases and are thought to occur at an early stage. Almost never do mutations arise in the loci of other Ras isoforms (Ha‐ and N‐), leading to the assumption that Ki‐Ras plays a unique role in tumorigenesis. In order to examine the distinctive function that Ki‐Ras plays in cancer development in the colon, we introduced constitutively active mutant Ki‐ and Ha‐Ras genes into an intermediate‐stage colon adenoma cell line (Caco‐2). We found that mutant active Ha‐RasV12 was more efficient at transforming these colon epithelial cells as assessed by anchorage‐independent growth, tumor formation in SCID mice and the development of mesenchymal morphology compared to transformation by Ki‐RasV12. We conducted microarray analysis in an attempt to reveal the genes whose aberrant expression is a direct result of overexpression of either Ki‐RasV12 or Ha‐RasV12. We used Clontech's Atlas cancer cDNA (588 genes) and RZPD's Onco Set 1 (1,544 genes) arrays. We identified fewer genes that were commonly regulated than were differentially expressed between Ki‐ and Ha‐RasV12 isoforms. Specifically, we found that Ki‐RasV12 regulated genes involved in cytokine signaling, cell adhesion and colon development, whereas Ha‐RasV12 mainly regulated genes involved in controlling cell morphology, correlating to an epithelial‐mesenchymal transition only observed in these cells. Our results demonstrate how 2 Ras isoforms regulate disparate biologic processes, revealing a number of genes whose deregulated expression may influence colon carcinogenesis (supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html ). © 2005 Wiley‐Liss, Inc." @default.
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• W2086177514 date "2005-11-29" @default.
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• W2086177514 title "Microarray analysis of the differential transformation mediated by Kirsten and Harvey Ras oncogenes in a human colorectal adenocarcinoma cell line" @default.
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• W2086177514 doi "https://doi.org/10.1002/ijc.21386" @default.
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