Steady state levels of transforming growth factor-beta1 and -beta2 mRNA and protein expression are elevated in colonic tumors in vivo irrespective of dietary lipids intervention.
Colonic tumors of human origin produce abundant transforming growth factor (TGF)-beta suggesting that TGF-beta is critical to their growth. Dietary lipids regulate a number of growth factors including TGF-beta. Whether elevated TGF-beta levels are consistently expressed in colonic tumors irrespective of the environmental milieu in an in vivo model is not known and forms the main objective of the present study. Male F344 rats were injected with azoxymethane, 10 weeks later, rats bearing preneoplastic lesions were fed a low fat (5% corn oil) diet and 3 high fat (5% corn oil with 18% corn oil, fish oil or beef tallow) diets for 16 weeks. Colonic tumors and mucosae were processed and assessed for TGF-beta status. TGF-beta1 and -beta2 mRNA levels were upregulated in colonic tumors more than in mucosae of all diet groups. Dietary lipids modulated TGF-beta mRNA in both tumors and mucosae, high corn and fish oil diets upregulated TGF-beta1 significantly more than the low fat corn oil or high fat beef tallow diets. Immunohistochemical assessments of tissues with different biological features revealed that TGF-beta1 and -beta2 were elevated in tumors and in selected microscopic preneoplastic lesions compared to normal mucosae. This is the first in vivo study, documenting that developing colonic tumors acquire upregulated TGF-beta phenotype even in the presence of lipid environments capable of differentially regulating TGF-beta in normal mucosae. Elevated expression of TGF-beta in a selected subset of microscopic preneoplastic lesions suggests that TGF-beta plays an important role on both early and late stages of colon carcinogenesis.
Raju
Jayadev
J
Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, R3T 2N2 Manitoba, Canada.
McCarthy
Brendan
B
Bird
Ranjana P
RP
D000818:Animals; D001397:Azoxymethane / Q000494:pharmacology; D001835:Body Weight; D002273:Carcinogens / Q000494:pharmacology; D002417:Cattle; D003110:Colonic Neoplasms / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology; D005395:Fish Oils / Q000494:pharmacology; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008297:Male; D008460:Meat; D008954:Models, Biological; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D015854:Up-Regulation; D003313:Zea mays
D002273:Carcinogens; D005395:Fish Oils; D012333:RNA, Messenger; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D001397:Azoxymethane