Steady state levels of transforming growth factor-β1 and -β2 mRNA and protein expression are elevated in colonic tumors in vivo irrespective of dietary lipids intervention

Abstract

Colonic tumors of human origin produce abundant transforming growth factor (TGF)-β suggesting that TGF-β is critical to their growth. Dietary lipids regulate a number of growth factors including TGF-β. Whether elevated TGF-β 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-β status. TGF-β1 and β2 mRNA levels were upregulated in colonic tumors more than in mucosae of all diet groups. Dietary lipids modulated TGF-β mRNA in both tumors and mucosae, high corn and fish oil diets upregulated TGF-β1 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-β1 and -β2 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-β phenotype even in the presence of lipid environments capable of differentially regulating TGF-β in normal mucosae. Elevated expression of TGF-β in a selected subset of microscopic preneoplastic lesions suggests that TGF-β plays an important role on both early and late stages of colon carcinogenesis. © 2002 Wiley-Liss, Inc.