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Results for “Intestinal Polyposis”

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At least 865 records · Page 48Linked to original sources
PubMed2001

Restoration of epithelial cell polarity in a colorectal cancer cell line by suppression of beta-catenin/T-cell factor 4-mediated gene transactivation.

Beta-catenin acts as a transcriptional coactivator by forming a complex with T-cell factor/lymphoid enhancer factor (TCF/LEF) DNA-binding proteins. Aberrant transactivation of a certain set of target genes by beta-catenin and TCF4 complexes has been implicated in familial and sporadic colorectal tumorigenesis. A colorectal cancer cell line, DLD-1, becomes irregularly multilayered, when maintained confluent for 2-3 weeks, and forms numerous dome-like polypoid foci piled-up over the surface of cell sheets. By the use of a strict tetracycline-regulation system, we found that the continuous suppression of beta-catenin/TCF4-mediated gene transactivation by dominant-negative TCF4B (deltaN30) reduced these piled-up foci and restored a simple monolayer of polarized columnar cells resembling normal intestinal epithelium. The restoration of epithelial cell polarity was evident in two ways: (a) the formation of microvilli over the apical surface; and (b) the distribution of a tight junction protein, ZO-1, to the lateral plasma membrane. Retroviral expression of stabilized beta-catenin (deltaN89) induced the formation of similar piled-up foci in untransformed IEC6 intestinal epithelial cells. Sulindac, a nonsteroidal antiinflammatory drug effective against colorectal tumorigenesis in familial adenomatous polyposis syndrome, suppressed the formation of foci. The loss of epithelial cell polarity may be a critical cellular event driving beta-catenin/TCF4-mediated intestinal tumorigenesis.

Adenocarcinoma↗
PubMed2004

Intestinal tumor progression is associated with altered function of KLF5.

Krüppel-like transcription factors have been linked to cell growth regulation and tumorigenesis in a number of systems. In the intestinal epithelium, expression of KLF5 (IKLF/BTEB2) is limited to proliferating crypt cells, indicating a growth-promoting role. Consistent with this role, we demonstrate that expression of KLF5 in non-transformed intestinal epithelial cells (ileal IEC-18 and Immorto-Min Colon Epithelial (IMCE) cells) enhances colony formation, cyclin D1 transcription, and cell growth. However, in contrast to these effects in non-transformed cells, KLF5 reduced colony number, failed to enhance cyclin D1 transcription, and was negatively correlated with cell growth in colon cancer cell lines. The relationship between tumor progression and KLF5 was further investigated using Ras-mediated transformation of IEC-18 and IMCE cells as syngeneic models. Ras-transformation recapitulated differences in the effects of KLF5 on cell growth and cyclin D1 transcription, providing a direct link between intestinal tumor progression and altered function of KLF5. Ras-transformation also markedly down-regulated KLF5; further analysis indicated that reduced expression of KLF5 mRNA and destabilization of KLF5 protein occur in intestinal tumors. Reduced levels of KLF5 mRNA were also detected in APC(min) mouse and human familial adenomatous polyposis adenomas compared with normal crypt epithelium, indicating that down-regulation of KLF5 is an early event in intestinal tumorigenesis in vivo. Collectively, these data indicate that intestinal tumor progression is associated with a change in the growth-related functions of KLF5 and that intestinal tumors down-regulate KLF5 expression by multiple mechanisms.

Adenoma↗
PubMed1979

Histogenesis of adenomatous polyps in the human large intestine.

Detailed histologic analyses have been performed in 75, minute, colorectal polyps from familial polyposis patients. All polyps were composed of typical adenomatous tissue, with, in addition, some normal-looking glands still to be found among the neoplastic elements. Bifurcating glands were not observed, and branching patterns were present in 27% of the polyps only. In 86% of the lesions, the number of gland openings along the polyp surface was larger than the number of gland bases observed along the muscularis mucosae. This difference increased with polyp size (r = 0.9043). Those data, together with previous radioautographic observations, suggest that formation of new adenomatous glands mainly results from an infolding of the surface epithelium between normal, preexisting glands. This mechanism sharply contrasts with villous polyps in which papillary projections arise upwards from the mucosal surface.

Cell Transformation, Neoplastic↗
PubMed2006

Gastric duodenal metaplasia in duodenal adenomas.

BACKGROUND: In cases of known aetiology, gastric duodenal metaplasia (GMD) is a reversible lesion. In cases of unknown aetiology, the fate of GMD remains elusive. GMD was recently found in a duodenal adenoma. AIM: To audit the frequency of GMD occurring in a cohort of duodenal adenomas. METHODS: Filed H&E-stained sections from 306 consecutive duodenal adenomas were investigated for the presence of GMD. RESULTS: 68% of the adenomas (n = 208) were from patients with familial adenomatous polyposis (FAP), and the remaining 32% (n = 98) were sporadic. GMD was found in 31.7% (66/208) of the duodenal FAP adenomas and in 59.2% (58/98) of the duodenal sporadic adenomas (p<0.05). The causes for this difference are elusive. CONCLUSIONS: As for other metaplasias of the gastrointestinal tract (intestinal metaplasia of the oesophagus and of the stomach, and metaplastic-hyperplastic polyposis of the colon, known to antedate neoplastic transformation), a subset of GMDs of unknown cause might be present in the duodenal mucosa before adenomatous changes ensue. That subset of GMD might have neoplastic proclivity similar to the metaplastic epithelium in other organs of the gastrointestinal tract. The known carcinogenic effect of high concentrations of bile acids and pancreatic juices bathing the duodenal mucosa carrying an irreversible subset of GDM might set aflame the adenomatous neoplastic transformation in these patients.

Adenoma↗
PubMedDate not supplied

Growth stimulation of intestinal tumours in Apc(Min/+) mice by dietary L-methionine supplementation.

We studied the effects of extra dietary methionine on the formation and growth of intestinal adenomas in the Min (Apc+/-) mouse, which is a murine model of the human familial adenomatous syndrome. The AIN-76A diet was supplemented with 0.7% L-methionine from week 4 after birth and the animals were killed at week 8. The number of tumours in Min mice was apparently not affected by the addition of extra methionine. However, the dietary methionine supplementation increased the surface area of small intestinal tumours by 41% (p=0.009). In the colon, extra methionine did not affect tumour size. In conclusion, extra dietary methionine promotes the growth of adenomas in the small intestine of Min mice.

Adenoma↗
PubMed2002

A Drosophila APC tumour suppressor homologue functions in cellular adhesion.

Adenomatous polyposis coli (APC) is an important tumour suppressor in the intestinal epithelium. Its function in reducing nuclear beta-catenin and T-cell factor (TCF)-mediated transcription is conserved from Drosophila to mammals. But APC proteins are also associated with the plasma membrane. Here, we show that mutational inactivation of Drosophila E-APC causes delocalization of Armadillo (the Drosophila beta-catenin) but not DE-cadherin from adhesive plasma membranes. Extensive gaps between these membranes are visible at the ultrastructural level. The oocyte is also mislocalized in E-APC mutant egg chambers, a phenotype that results from a failure of cadherin-based adhesion. These results indicate that Drosophila APC functions in cellular adhesion; these results could have implications for colorectal adenoma formation and tumour progression in humans.

Adenomatous Polyposis Coli↗