Expression of transforming growth factor beta1 and its type II receptor in mouse colon tumors induced by azoxymethane.
Alterations in transforming growth factor beta1 (TGF-beta1) and its type II receptor (TbetaR-II) have been implicated in the pathogenesis of a variety of human cancers and animal tumor models. We postulated that TGF-beta1 and TbetaR-II alterations may also be involved in mouse colon tumorigenesis induced by the chemical carcinogen, azoxymethane (AOM). In the present study, normal colon tissues and AOM-induced colon tumors from SWR/J mice were analyzed for mutational changes in the TbetaR-II gene, and the expression and localization of TGF-beta1 and TbetaR-II were examined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemisty. Direct DNA sequencing of the coding sequence of the TbetaR-II gene revealed no mutational changes in tumors induced by AOM when compared with the sequence from normal colon tissue. However, TGF-beta1 and TbetaR-II mRNA levels in tumor samples were increased 1.8-fold (p<0.01) and 1.3-fold (p<0.01), respectively, when compared with control mouse colon tissue. The results of immunohistochemical analysis of TGF-beta1 and TbetaR-II were correlated with mRNA expression data. An increase in staining intensity of both TGF-beta and TbetaR-II were observed in colon tumors. These findings suggest that alterations in the expression of TGF-beta1 and TbetaR-II may be involved in the pathogenesis of colon tumors induced by AOM in mice.
Wang
Q S
QS
BioGenex Laboratories, San Ramon, CA 94583, USA.
Guda
K
K
Papanikolaou
A
A
Dong
M
M
Rosenberg
D W
DW
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D003062:Codon / Q000235:genetics; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D017354:Point Mutation; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D053773:Transforming Growth Factor beta1
D002273:Carcinogens; D003062:Codon; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D001397:Azoxymethane