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- Dimberg, Jan, et al.
(författare)
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Enhanced expression of cyclooxygenase-2 and nuclear beta-catenin are related to mutations in the APC gene in human colorectal cancer
- 2001
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 21:2A, s. 911-915
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Tidskriftsartikel (refereegranskat)abstract
- Mutational inactivation of the human tumour suppressor gene adenomatous polyposis coli (APC) results in constitutive activation of beta -catenin/T cell factor-4 (Tcf-4) mediated transcription of target genes. Up-regulation of cyclooxygenase-2 (COX-2) protein is frequently found in human colorectal cancer (CRC). We analysed 38 CRC for mutations in APC and beta -catenin and found an association between APC mutations and elevated COX-2 levels. Furthermore, APC mutations were predominantly observed in tumour tissues from the rectum compared to tumours of colonic origin. Western blot analysis revealed that nuclear beta -catenin levels were generally higher in tumours with APC mutations compared to tumours with wild type APC. However, there was also a higher level of nuclear beta -catenin in tumour compared to normal tissue, hut nuclear Tcf-4 protein was constitutively expressed in tumour and normal tissue and showed no differences. An identified putative Tcf-4 binding element in the COX-2 promoter may partly explain the enhanced level of COX-2 and support the idea that COX-2 may be a downstream target of the APC/beta -catenin/Tcf-4 pathway.
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- Monstein, Hans-Jürg, et al.
(författare)
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K-ras and B-raf gene mutations are not associated with gastrin- and CCK2-receptor mRNA expression in human colorectal tumour tissues
- 2004
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 34:2, s. 100-106
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colorectal cancer is a multistep process caused by genetic alterations in cell growth regulatory genes such as K-ras and B-raf. It has been assumed that mutations in the K-ras gene induce gastrin gene expression and that gastrin stimulates the growth of colorectal cancer in an autocrine fashion by coexpressing gastrin and cholecystokinin (CCK)2 receptors. The aim of this study was to examine a possible association of K-ras and B-raf gene mutations with gastrin and CCK2 receptor mRNA expression in human colon and rectum tumour biopsy specimens. Methods: K-ras and B-raf gene mutations as well as gastrin and CCK2 receptor mRNA expression in 50 colon and 46 rectum biopsies, respectively, were determined using molecular biology methods. Results: K-ras mutations occurred in 44% colon and 30% rectum and B-raf mutations in 16% colon and 4% rectum tumours, respectively. Gastrin mRNA was expressed in 64% colon and 61% rectum tumours, whereas CCK2 receptor mRNAs was expressed in 32% colon and 13% rectum tumours. K-ras or B-raf gene mutations and simultaneous gastrin mRNA expression was observed in 40% colon and 17% rectum tumours, respectively. Coexpression of gastrin and CCK2 receptor mRNA occurred in 20% colon and 9% rectal tumours. Conclusions: The results do not support the hypothesis that K-ras and B-raf gene mutations have an impact on gastrin- and CCK-receptor mRNA expression in colorectal tumour tissues.
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