Lactoferrin modifies apoptosis-related gene expression in the colon of the azoxymethane-treated rat.
Lactoferrin, an iron-binding glycoprotein, exhibits suppressive effects on development of azoxymethane (AOM)-induced tumors in the rat colon, but the mechanisms are largely unknown. In this study, we investigated the effect of lactoferrin on the gene expression of 10 apoptosis-related molecules in colon mucosa of AOM-treated rats during early and late stages of colon carcinogenesis by reverse transcription PCR. Here we document that a death-inducing receptor, Fas, and a pro-apoptotic Bcl-2 family member, Bid, are increased in the colon mucosa in proportion to decreases in AOM-induced aberrant crypt foci by lactoferrin. Similarly, increased expression of the pro-apoptotic Bcl-2 family member, Bax, was also observed in AOM-induced tumors in rats fed by lactoferrin. These results indicate that Fas and pro-apoptotic Bcl-2 members participate in the lactoferrin action and may contribute to suppressive effects on tumor development in the rat colon.
Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. kefujita@gan2.res.ncc.go.jp
Ken-ichi
K
Fujita
Eiji
E
Matsuda
Kazunori
K
Sekine
Masaaki
M
Iigo
Hiroyuki
H
Tsuda
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D001397:Azoxymethane / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic; D018890:Chemoprevention; D003110:Colonic Neoplasms / Q000235:genetics / Q000503:physiopathology* / Q000662:veterinary; D019938:Cyclin D1 / Q000096:biosynthesis*; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000187:drug effects*; D007781:Lactoferrin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D015854:Up-Regulation
D002273:Carcinogens; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D019938:Cyclin D1; D007781:Lactoferrin; D001397:Azoxymethane