Reference SummaryErik Paulsen J, Cancer Res 2001 Jul 1;61(13):5010-5

Title

Qualitative and Quantitative Relationship between Dysplastic Aberrant Crypt Foci and Tumorigenesis in the Min/+ Mouse Colon.

Authors

Erik Paulsen J; Steffensen IL; Loberg EM; Husoy T; Namork E; Alexander J

Journal

Cancer Res

Volume

Issue

Year

2001

Pages

5010-5

Abstract

The multiple intestinal neoplasia (Min)/+ mouse, which harbors only one functional allele of the Apc gene, is susceptible to environmental factors that disrupt this gene and subsequently trigger Apc-driven tumorigenesis in the colon. Aberrant crypt foci (ACF) are assumed to be preneoplastic lesions in colon carcinogenesis. Recently, we reported the absence of 'classical' ACF in the colon of untreated Min/+ mice. Instead we identified flat dysplastic lesions, which we denoted ACF(Min) (J. E. Paulsen et al., Scand. J. Gastroenterol., 35: 534-539, 2000). In contrast to the classical type, ACF(Min) are not elevated above the surrounding mucosa, and their detection is totally dependent on methylene blue staining and transillumination. In the present study, we treated Min/+ mice with 5 mg/kg body weight azoxymethane (AOM) at weeks 1 and 2 and demonstrated induction of both types of lesions. However, only ACF(Min) appeared to be associated with the development of adenomas. Monocryptal ACF(Min), large ACF(Min), and adenomas showed a uniform histopathological picture of dysplasia and cytoplasmic overexpression of beta-catenin, indicating a qualitative relationship between these lesions. Also a quantitative relationship was suggested because the dramatic decrease in ACF(Min) number from week 7 to 11 was paralleled by a reciprocal increase in tumor number, indicating fast-crypt multiplication of ACF(Min). In AOM-treated +/+ (wild-type) littermates, a low number of ACF(Min) and tumors with the same characteristics as in Min/+ mice was seen. In contrast to ACF(Min), histopathological and immunohistochemical examination of classical ACF showed normal or hyperplastic crypts with normal levels of beta-catenin expression. In AOM-treated Min/+ mice, the number of classical ACF was virtually constant from week 7 to 11, and only a modest increase of crypt multiplicity was observed. The number of AOM-induced classical ACF at week 11 was not different in Min/+ mice and +/+ mice. In conclusion, we identified two distinct populations of altered crypts in the colon of Min/+ mice after AOM treatment. The ACF(Min), which resemble the dysplastic ACF described previously, clearly showed a continuous development from the monocryptal stage to adenoma, and they were characterized by fast-growing crypts with altered control of beta-catenin. In contrast, the classical ACF, which resemble the hyperplastic ACF described previously, were characterized by slow-growing crypts with normal beta-catenin expression, and they were probably not related to tumorigenesis.

Links

J:70170 – MGI References
11431334 – National Library of Medicine/PubMed

Strain Notes

Strain	Note
C57BL/6J	Mice were bred at the National Institute of Public Health, Oslo, Norway. C57BL/6J-Apc^Min/+ mice were originally purchased from The Jackson Laboratory, and bred inhouse to C57BL/6J wild type females.
C57BL/6J-Apc^Min/+	Mice were bred at the National Institute of Public Health, Oslo, Norway. C57BL/6J-Apc^Min/+ mice were originally purchased from The Jackson Laboratory, and bred inhouse to C57BL/6J wild type females.

Models
Strain	Model Name	Treatment Agent(s)	Organ Affected	Frequency
C57BL/6J-Apc^Min/+	Intestine - Large Intestine - Colon adenoma	azoxymethane (AOM)	Intestine - Large Intestine - Colon	observed
C57BL/6J-Apc^Min/+	Intestine - Large Intestine - Colon adenoma		Intestine - Large Intestine - Colon	observed
C57BL/6J	Intestine - Large Intestine - Colon adenoma		Intestine - Large Intestine - Colon	0
C57BL/6J	Intestine - Large Intestine - Colon adenoma	azoxymethane (AOM)	Intestine - Large Intestine - Colon	0 - observed
C57BL/6J-Apc^Min/+	Intestine - Large Intestine - Colon dysplasia	azoxymethane (AOM)	Intestine - Large Intestine - Colon	observed
C57BL/6J-Apc^Min/+	Intestine - Large Intestine - Colon foci - aberrant crypt (ACF)	azoxymethane (AOM)	Intestine - Large Intestine - Colon	observed
C57BL/6J-Apc^Min/+	Intestine - Large Intestine - Colon foci - aberrant crypt (ACF)		Intestine - Large Intestine - Colon	0 - observed
C57BL/6J	Intestine - Large Intestine - Colon foci - aberrant crypt (ACF)		Intestine - Large Intestine - Colon	0
C57BL/6J	Intestine - Large Intestine - Colon foci - aberrant crypt (ACF)	azoxymethane (AOM)	Intestine - Large Intestine - Colon	observed
C57BL/6J-Apc^Min/+	Intestine - Large Intestine - Colon hyperplasia	azoxymethane (AOM)	Intestine - Large Intestine - Colon	observed