Increased levels of PPARbeta/delta and cyclin D1 in flat dysplastic ACF and adenomas in Apc(Min/+) mice

TY - JOUR

T1 - Increased levels of PPARbeta/delta and cyclin D1 in flat dysplastic ACF and adenomas in Apc(Min/+) mice

AU - Knutsen, Helle K

AU - Olstørn, Hege B

AU - Paulsen, Jan Erik

AU - Husøy, Trine

AU - Goverud, Ingeborg L

AU - Løberg, Else Marit

AU - Kristiansen, Karsten

AU - Alexander, Jan

PY - 2005

Y1 - 2005

N2 - Background: In ApcMin/+ (Min; multiple intestinal neoplasia) mice two separate populations of aberrant crypt foci (ACF) develop in the colon after azoxymethane (AOM) exposure. ACFMin' with a flat appearance, severe dysplasia and increased β-catenin expression, are related to adenoma development, whereas classic ACF, with elevated structure, hyperplasia and normal β-catenin level, are probably not. Materials and Methods: The expressions of peroxisome proliferator-activated receptors (PPARs) β/δ, cyclin D1 and β-catenin in ACF, adenoma and normal tissue from AOM-treated ApcMin/+ mice and a familial adenomatous polyposis (FAP) patient colon tumour were assessed by immunohistochemistry and immunoblotting. Results: The flat ACF (ACFMin) displayed increased cytoplasmic levels of β-catenin, and increased levels of cyclin D1 and PPARβ/δ. In contrast, the expression in classic ACF resembled normal mucosa. Adenomas from ApcMin/+ mice, as well as a FAP patient colon tumour, displayed increased nuclear and cytoplasmic levels of β-catenin, and the same expression patterns of cyclin D1 and PPARβ/δ as those found in flat ACF. Conclusion: In addition to activation of the Wnt signalling pathway in both flat ACF and in adenomas in ApcMin/+ mice, the increased expression of PPARβ/δ in these lesions could be a target for pro-inflammatory signals important for growth and reduced apoptosis.

AB - Background: In ApcMin/+ (Min; multiple intestinal neoplasia) mice two separate populations of aberrant crypt foci (ACF) develop in the colon after azoxymethane (AOM) exposure. ACFMin' with a flat appearance, severe dysplasia and increased β-catenin expression, are related to adenoma development, whereas classic ACF, with elevated structure, hyperplasia and normal β-catenin level, are probably not. Materials and Methods: The expressions of peroxisome proliferator-activated receptors (PPARs) β/δ, cyclin D1 and β-catenin in ACF, adenoma and normal tissue from AOM-treated ApcMin/+ mice and a familial adenomatous polyposis (FAP) patient colon tumour were assessed by immunohistochemistry and immunoblotting. Results: The flat ACF (ACFMin) displayed increased cytoplasmic levels of β-catenin, and increased levels of cyclin D1 and PPARβ/δ. In contrast, the expression in classic ACF resembled normal mucosa. Adenomas from ApcMin/+ mice, as well as a FAP patient colon tumour, displayed increased nuclear and cytoplasmic levels of β-catenin, and the same expression patterns of cyclin D1 and PPARβ/δ as those found in flat ACF. Conclusion: In addition to activation of the Wnt signalling pathway in both flat ACF and in adenomas in ApcMin/+ mice, the increased expression of PPARβ/δ in these lesions could be a target for pro-inflammatory signals important for growth and reduced apoptosis.

M3 - Journal article

C2 - 16309164

SN - 0250-7005

VL - 25

SP - 3781

EP - 3789

JO - Anticancer Research

JF - Anticancer Research

IS - 6B

ER -