RRC ID 28828
著者 Igarashi M, Hippo Y, Ochiai M, Fukuda H, Nakagama H.
タイトル AKT is critically involved in cooperation between obesity and the dietary carcinogen amino-1-methyl-6-phenylimidazo [4,5-b] (PhIP) toward colon carcinogenesis in rats.
ジャーナル Biochem Biophys Res Commun
Abstract Obesity is highly associated with colon cancer development. Whereas it is generally attributed to pro-tumorigenic effects of high fat diet (HFD), we here show that a common genetic basis for predisposition to obesity and colon cancer might also underlie the close association. Comparison across multiple rat strains revealed that strains prone to colon tumorigenesis initiated by a dietary carcinogen amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) tended to develop obesity. Through transcriptome and extensive immunoblotting analyses, we identified the basal level of activated AKT in colonic crypts as a biomarker for the common predisposition. Notably, PhIP induced activation of AKT, which could persist for several weeks under a low fat diet (LFD), but not under HFD. On the other hand, PhIP and HFD independently induced Wnt pathway activation and inhibited apoptosis, through distinct mechanisms involving GSK-3β, caspase 3 and poly-ADP ribose polymerase (PARP). Taken together, these observations provide mechanistic insights into how PhIP-induced activation of AKT might cooperate with HFD at multiple levels toward development of colon cancer.
巻・号 443(3)
ページ 852-7
公開日 2014-1-17
DOI 10.1016/j.bbrc.2013.12.059
PII S0006-291X(13)02128-1
PMID 24342614
MeSH Aberrant Crypt Foci / metabolism Aberrant Crypt Foci / pathology Animals Apoptosis / drug effects Carcinogenesis / drug effects Carcinogenesis / pathology* Carcinogens / toxicity* Cell Line Colon / drug effects Colon / enzymology Colon / pathology Colonic Neoplasms / enzymology* Colonic Neoplasms / pathology Diet* Diet, High-Fat Disease Susceptibility / pathology Enzyme Activation / drug effects Humans Imidazoles / toxicity* Male Obesity / enzymology* Obesity / pathology Phosphorylation / drug effects Proto-Oncogene Proteins c-akt / metabolism* Rats Rats, Inbred F344 Wnt Signaling Pathway / drug effects
IF 2.985
引用数 4
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ラット PVG/Seac(strainID=113) DON/Kyo(strainID=1) LEA/Hok(strainID=70) DRH/Seac(strainID=111) WF/Kop(strainID=510) SDJ/Hok(strainID=74) LE/Stm(strainID=265) NIG-III/Hok(strainID=73)