The role of mutant Apc in the development of dysplasia and cancer in the mouse model of dextran sulfate sodium–induced colitis

Cooper, Harry S.; Everley, Lynette C.; Chang, Wen‐Chi L.; Pfeiffer, Gordon R.; Lee, Bryan; Murthy, Shubha; Clapper, Margie L.

doi:10.1053/gast.2001.29609

Cited by 95 publications

(85 citation statements)

References 31 publications

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“…2a,b), indicating that dysplastic crypts 43 or adenomatous lesions 41 are precursor lesions for colon carcinoma and DSS treatment could promote their growth. The findings support an earlier report by Cooper et al, 14 but their incidence of colonic cancer was low: 22% in Min mice exposed to 1-cycle of DSS (administration 4% DSS for 4 days and H 2 O for 17 days) and 40% in Min mice exposed to 2-cycle of DSS. The discrepancy existing in these 2 studies may be due to the differences in the treatment period and the dose and molecular weight of DSS.…”

Section: Discussionsupporting

confidence: 91%

“…However DSS treatment did not induce preneoplastic and neoplastic lesions in the large bowel wild-type (Apc 1/1 ) mice of either sex. This report describing rapid development of a number of colonic neoplasms in Apc Min/1 mice within a short-term period (5 weeks) support an earlier work by Cooper et al, 14 who found that treatment with 2 cycles of 4% DSS results in 40% incidence of colon cancer with a multiplicity of 0.6760.27 in female Min mice at 42 days. Our findings suggest that the development of colonic dysplastic crypts and/or neoplasms in the short-term (up to 5 weeks) needs both the gene (Apc) mutation and subsequent inflammatory stimuli, but not either alone under the current exper- imental condition.…”

Section: Discussionsupporting

confidence: 89%

“…They also reported the development of colon cancer in 60-day-old Apc Min/1 mice that received 4% DSS alone. 14 In addition, Barbour et al 15 suggested that a relationship between chronic inflammation and small intestinal tumorigenesis in Apc Min/1 mice.…”

Section: Abstract: Apcmentioning

confidence: 99%

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Dextran sodium sulfate strongly promotes colorectal carcinogenesis in Apc^Min/+ mice: Inflammatory stimuli by dextran sodium sulfate results in development of multiple colonic neoplasms

Tanaka¹,

Kohno²,

Suzuki³

et al. 2005

Intl Journal of Cancer

153

149

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mouse, contains a truncating mutation in the Apc gene and spontaneously develops numerous adenomas in the small intestine but few in the large bowel. Our study investigated whether dextran sodium sulfate (DSS) treatment promotes the development of colonic neoplasms in Apc Min/1 mice. Apc Min/1 and Apc 1/1 mice of both sexes were exposed to 2% dextran sodium sulfate in drinking water for 7 days, followed by no further treatment for 4 weeks. Immunohistochemistry for cyclooxygenase-2, inducible nitric oxide synthase, b-catenin, p53, and nitrotyrosine, and mutations of b-catenin and K-ras and loss of wild-type allele of the Apc gene in the colonic lesions were examined. Sequential observation of female ApcMin/1 mice that received DSS was also performed up to week 5. At week 5, numerous colonic neoplasms developed in male and female Apc Min/1 mice but did not develop in Apc 1/1 mice. Adenocarcinomas developed in Apc Min/1 mice that received DSS showed loss of heterozygosity of Apc and no mutations in the b-catenin and K-ras genes. The treatment also significantly increased the number of small intestinal polyps. Sequential observation revealed increase in the incidences of colonic neoplasms and dysplastic crypts in female Apc Min/1 mice given DSS. DSS treatment increased inflammation scores, associated with high intensity staining of b-catenin, cyclooxygenase-2, inducible nitric oxide synthase and nitrotyrosine. Interestingly, strong nuclear staining of p53 was specifically observed in colonic lesions of Apc Min/1 mice treated with DSS. Our results suggest a strong promotion effect of DSS in the intestinal carcinogenesis of Apc Min/1 mice. The findings also suggest that strong oxidative/nitrosative stress caused by DSS-induced inflammation may contribute to the colonic neoplasms development. ' 2005 Wiley-Liss, Inc.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 89%

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Dextran sodium sulfate strongly promotes colorectal carcinogenesis in Apc^Min/+ mice: Inflammatory stimuli by dextran sodium sulfate results in development of multiple colonic neoplasms

Tanaka¹,

Kohno²,

Suzuki³

et al. 2005

Intl Journal of Cancer

153

149

View full text Add to dashboard Cite

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“…Alterations of this pathway are mostly caused by inactivation of the APC gene, which is a frequent and early genetic event in sporadic colorectal carcinogenesis. Studies of UC-associated dysplasia and cancer in humans have reported various degrees of loss of function of APC [22][23][24][25][26]. The reported frequency of APC mutations in UC-related neoplasia has varied from 0% to 6% [27] and up to 50% [23] in several small studies.…”

Section: Discussionmentioning

confidence: 99%

Associations between Markers of Colorectal Cancer Stem Cells, Mutations, Mirna, and Clinical Characteristics of Ulcerative Colitis

Liu¹,

Levi²

2016

Transl Med (sunnyvale)

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“…However, even with the extended lifespan, colonic adenomas in this mouse do not progress to cancer, unless a stimulus such as DSS is administered. 42, 43 Halberg et al 21 crossed B6 Min/1 males with C57BR/cdcJ females producing Min/1 hybrids with a mean lifespan of 232 days. However, these F1 hybrids exhibited a considerable reduction in number of intestinal tumors, with, on average, only 19 tumors recorded in the entire intestinal tract.…”

Section: Molecular Cancer Biologymentioning

confidence: 99%

Spontaneous initiation, promotion and progression of colorectal cancer in the novel A/J Min/+ mouse

Södring

Gunnes

Paulsen

2015

Intl Journal of Cancer

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The C57BL/6J multiple intestinal neoplasia (Min/1) mouse is a widely used murine model for familial adenomatous polyposis, a hereditary form of human colorectal cancer. However, it is a questionable model partly because the vast majority of tumors arise in the small intestine, and partly because the fraction of tumors that progress to invasive carcinomas is minuscule. A/J mice are typically more susceptible to carcinogen-induced colorectal cancer than C57BL/6J mice. To investigate whether the novel Min/1 mouse on the A/J genetic background could be a better model for colorectal cancer, we examined the spontaneous intestinal tumorigenesis in 81 A/J Min/1 mice ranging in age from 4 to 60 weeks. The A/J Min/1 mouse exhibited a dramatic increase in number of colonic lesions when compared to what has been reported for the conventional Min/1 mouse; however, an increase in small intestinal lesions did not occur. In addition, this novel mouse model displayed a continual development of colonic lesions highlighted by the transition from early lesions (flat ACF) to tumors over time. In mice older than 40 weeks, 13 colonic (95% CI: 8.7-16.3) and 21 small intestinal (95% CI: 18.6-24.3) tumors were recorded. Notably, a considerable proportion of those lesions progressed to carcinomas in both the colon (21%) and small intestine (51%). These findings more closely reflect aspects of human colorectal carcinogenesis. In conclusion, the novel A/J Min/1 mouse may be a relevant model for initiation, promotion and progression of colorectal cancer.Colorectal cancer is the third most common cancer worldwide and accounted for approximately 1.4 million new cases and close to 700,000 deaths in 2012. Incidence rates are slightly higher in men than in women, and this cancer becomes increasingly more common with age.1 One of the most common inherited colorectal cancer syndromes is familial adenomatous polyposis (FAP), which is caused by germline mutations in the tumor-suppressor gene adenomatous polyposis coli (APC). 2,3 FAP patients inherit a mutated APC allele and when the second allele is inactivated by mutation, a large number of adenomas develop in the colon. 4 Inactivation of the second APC allele leads to reduced degradation of b-catenin and activation of the canonical Wnt signaling pathway, which in turn leads to dysplasia. 5,6 Mutation in one APC allele followed by mutation in, or loss of, the second allele is also apparent in 80% of sporadic colorectal cancer cases. 7 In humans, most colorectal cancers progress slowly, taking anywhere from 5 to 20 years for early colonic lesions to develop into benign adenomas, and an additional 5 to 15 years for those adenomas to develop into malignant carcinomas. 8,9One of the most frequently used murine models for colorectal cancer is the multiple intestinal neoplasia (Min/1) mouse (Mus musculus). This particular mouse model was discovered after a random mutation by the mutagen ethylnitrosourea caused spontaneous formation of adenomas throughout the intestinal tract.10 Similar to the mutation see...

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The role of mutant Apc in the development of dysplasia and cancer in the mouse model of dextran sulfate sodium–induced colitis

Cited by 95 publications

References 31 publications

Dextran sodium sulfate strongly promotes colorectal carcinogenesis in Apc^Min/+ mice: Inflammatory stimuli by dextran sodium sulfate results in development of multiple colonic neoplasms

Dextran sodium sulfate strongly promotes colorectal carcinogenesis in Apc^Min/+ mice: Inflammatory stimuli by dextran sodium sulfate results in development of multiple colonic neoplasms

Associations between Markers of Colorectal Cancer Stem Cells, Mutations, Mirna, and Clinical Characteristics of Ulcerative Colitis

Spontaneous initiation, promotion and progression of colorectal cancer in the novel A/J Min/+ mouse

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The role of mutant Apc in the development of dysplasia and cancer in the mouse model of dextran sulfate sodium–induced colitis

Cited by 95 publications

References 31 publications

Dextran sodium sulfate strongly promotes colorectal carcinogenesis in ApcMin/+ mice: Inflammatory stimuli by dextran sodium sulfate results in development of multiple colonic neoplasms

Dextran sodium sulfate strongly promotes colorectal carcinogenesis in ApcMin/+ mice: Inflammatory stimuli by dextran sodium sulfate results in development of multiple colonic neoplasms

Associations between Markers of Colorectal Cancer Stem Cells, Mutations, Mirna, and Clinical Characteristics of Ulcerative Colitis

Spontaneous initiation, promotion and progression of colorectal cancer in the novel A/J Min/+ mouse

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Dextran sodium sulfate strongly promotes colorectal carcinogenesis in Apc^Min/+ mice: Inflammatory stimuli by dextran sodium sulfate results in development of multiple colonic neoplasms

Dextran sodium sulfate strongly promotes colorectal carcinogenesis in Apc^Min/+ mice: Inflammatory stimuli by dextran sodium sulfate results in development of multiple colonic neoplasms