ApcMin: A mouse model for intestinal and mammary tumorigenesis

Moser, Amy R.; Luongo, Cindy; Gould, Karen A.; McNeley, M.K; Shoemaker, Alexander R.; Dove, William F.

doi:10.1016/0959-8049(95)00181-h

Cited by 265 publications

(212 citation statements)

References 21 publications

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“…The Min mouse, which has a germ-line mutation in one allele of the APC tumor suppressor gene, is a well characterized model for human familial adenomatous polyposis (32). Administration of the analog for 9 weeks reduced the formation of colon and small intestinal polyps by 42% as effectively as the nonsteroidal antiinflammatory agent Sulindac (Table 1), which has consistently demonstrated efficacy in this model (33).…”

Section: Icg-001 Treatment Reduces the Steady-state Levels Of Survivimentioning

confidence: 99%

A small molecule inhibitor of β-catenin/cyclic AMP response element-binding protein transcription

Emami

Nguyen

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

807

843

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Inherited and somatic mutations in the adenomatous polyposis coli occur in most colon cancers, leading to activation of β-catenin-responsive genes. To identify small molecule antagonists of this pathway, we challenged transformed colorectal cells with a secondary structure-templated chemical library, looking for compounds that inhibit a β-catenin-responsive reporter. We identified ICG-001, a small molecule that down-regulates β-catenin/T cell factor signaling by specifically binding to cyclic AMP response element-binding protein. ICG-001 selectively induces apoptosis in transformed cells but not in normal colon cells, reduces in vitro growth of colon carcinoma cells, and is efficacious in the Min mouse and nude mouse xenograft models of colon cancer.

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Section: Icg-001 Treatment Reduces the Steady-state Levels Of Survivimentioning

confidence: 99%

A small molecule inhibitor of β-catenin/cyclic AMP response element-binding protein transcription

Emami

Nguyen

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

807

843

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“…Mutations in APC, a negative regulator of the Wnt signaling pathway, have been reported to confer an increased risk for development of breast cancer in Ashkenzi Jews (Redston et al, 1998;Woodage et al, 1998). Min mice, which carry a nonsense mutation at one APC locus, also have increased risk for mammary carcinomas after carcinogen treatment (Moser et al, 1993(Moser et al, , 1995. With the use of additional TG mice, it will be interesting to determine if deregulated expression of other components of the Wnt-1 signaling pathway, such as over-expression of bcatenin and inactivation of E-cadherin, also induce mammary tumors.…”

Section: Involvement Of Other Components Of the Wnt Signaling Pathwaymentioning

confidence: 99%

Use of MMTV-Wnt-1 transgenic mice for studying the genetic basis of breast cancer

2000

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Wnt-1 was ®rst identi®ed as a protooncogene activated by viral insertion in mouse mammary tumors. Transgenic expression of this gene using a mouse mammary tumor virus LTR enhancer causes extensive ductal hyperplasia early in life and mammary adenocarcinomas in approximately 50% of the female transgenic (TG) mice by 6 months of age. Metastasis to the lung and proximal lymph nodes is rare at the time tumors are detected but frequent after the removal of the primary neoplasm. The potent mitogenic e ect mediated by Wnt-1 expression does not require estrogen stimulation; tumors form after an increased latency in estrogen receptor a-null mice. Several genetic lesions, including inactivation of p53 and over-expression of Fgf-3, collaborate with Wnt-1 in leading to mammary tumors, but loss of Sky and inactivation of one allele of Rb do not a ect the rate of tumor formation in Wnt-1 TG mice.

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“…First, desmoid tumours have been reported to occur spontaneously in Apc mutant mice (Shoemaker et al, 1997;Smits et al, 1998). Second, Apc Min heterozygotes show an increased susceptibility to mammary carcinoma both spontaneously and following genotoxic stress such as carcinogen treatment or X irradiation (Moser et al, 1993(Moser et al, , 1995van der Houven et al, 1997). Finally, Apc heterozygosity on a p53 null background has been shown to strongly predispose to pancreatic neoplasia (Clarke et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Dysregulated expression of β-catenin marks early neoplastic change in Apc mutant mice, but not all lesions arising in Msh2 deficient mice

Kongkanuntn¹,

Bubb²,

Sansom³

et al. 1999

Oncogene

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We have analysed the pattern of b-catenin expression by immunohistochemistry in mice singly or multiply mutant for Apc, p53 and Msh2. We observed increased expression of b-catenin in all intestinal lesions arising on an Apc Min +/7 background. In all categories of lesion studied mosaic patterns of b-catenin expression were observed, with the proportion of cells showing enhanced expression decreasing with increasing lesion size. p53 status did not alter these patterns. We also show that bcatenin dysregulation marks pancreatic abnormalities occurring in Apc Min +/7 and (Apc Min +/7, p537/7) mice. In these mice both adenomas and adenocarcinomas of the pancreas arose and were characterized by increased expression of b-catenin. We have extended these analyses to intestinal lesions arising in mice mutant for the mismatch repair gene Msh2. In these mice, increased expression of b-catenin was again observed. However, in contrast with Apc Min +/7 mice, a subset of lesions retained normal expression. Taken together, these ®ndings show that increased expression of b-catenin is an e cient marker of early neoplastic change in both murine intestine and pancreas in Apc mutant mice. However, we also show that dysregulation of b-catenin is not an obligate step in the development of intestinal lesions, and therefore that genetic events other than the loss of Apc function may initiate the transition from normal to neoplastic epithelium.

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ApcMin: A mouse model for intestinal and mammary tumorigenesis

Cited by 265 publications

References 21 publications

A small molecule inhibitor of β-catenin/cyclic AMP response element-binding protein transcription

A small molecule inhibitor of β-catenin/cyclic AMP response element-binding protein transcription

Use of MMTV-Wnt-1 transgenic mice for studying the genetic basis of breast cancer

Dysregulated expression of β-catenin marks early neoplastic change in Apc mutant mice, but not all lesions arising in Msh2 deficient mice

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