Increased levels of PPARbeta/delta and cyclin D1 in flat dysplastic ACF and adenomas in Apc(Min/+) mice.
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 beta-catenin expression, are related to adenoma development, whereas classic ACF, with elevated structure, hyperplasia and normal beta-catenin level, are probably not.


METHODS
The expressions of peroxisome proliferator-activated receptors (PPARs) beta/delta, cyclin D1 and beta-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 beta-catenin, and increased levels of cyclin D1 and PPARbeta/delta. 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 beta-catenin, and the same expression patterns of cyclin D1 and PPARbeta/delta as those found in flat ACF.


CONCLUSIONS
In addition to activation of the Wnt signalling pathway in both flat ACF and in adenomas in Apc(Min/+) mice, the increased expression of PPARbeta/delta in these lesions could be a target for pro-inflammatory signals important for growth and reduced apoptosis.
Knutsen
Helle K
HK
Department of Food Toxicology, Norwegian Institute of Public Health, Oslo, Norway. helleknutsen@fhi.no
Olstørn
Hege B
HB
Paulsen
Jan Erik
JE
Husøy
Trine
T
Goverud
Ingeborg L
IL
Løberg
Else Marit
EM
Kristiansen
Karsten
K
Alexander
Jan
J
D000236:Adenoma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001397:Azoxymethane; D002273:Carcinogens; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D019938:Cyclin D1 / Q000096:biosynthesis*; D017491:Genes, APC; D006965:Hyperplasia; D015151:Immunoblotting; D051379:Mice; D047494:PPAR delta / Q000096:biosynthesis*; D048068:PPAR-beta / Q000096:biosynthesis*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000096:biosynthesis
D002273:Carcinogens; D047494:PPAR delta; D048068:PPAR-beta; D051176:beta Catenin; D019938:Cyclin D1; D001397:Azoxymethane