Increased Levels of PPARβ/δ and Cyclin D1 in Flat Dysplastic ACF and Adenomas in ApcMin/+ Mice

• Published in: Anticancer research 2005-11, Vol.25 (6B), p.3781
• Main Authors: HELLE K. KNUTSEN, HEGE B. ØLSTØRN, JAN ERIK PAULSEN, TRINE HUSØY, INGEBORG L. GOVERUD, ELSE MARIT LØBERG, KARSTEN KRISTIANSEN, JAN ALEXANDER
• Format: Article
• Language: English
• ISSN: 0250-7005; 1791-7530

Background: In Apc Min/+ (Min; multiple intestinal neoplasia) mice two separate populations of aberrant crypt foci (ACF) develop in the colon after azoxymethane (AOM) exposure. ACF Min , 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 Apc Min/+ mice and a familial adenomatous polyposis (FAP) patient colon tumour were assessed by immunohistochemistry and immunoblotting. Results: The flat ACF (ACF Min ) 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 Apc Min/+ 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 Apc Min/+ mice, the increased expression of PPARβ/δ in these lesions could be a target for pro-inflammatory signals important for growth and reduced apoptosis.