セッション情報 シンポジウム9

疾患モデル動物を用いた消化器病研究の最前線

タイトル

S9-2 Cytoglobin-deficient mice―a novel animal model to study liver and lung carcinogeneis

演者 Thi Thanh Thuy Le(大阪市立大学大学院医学研究科肝胆膵病態内科学)
共同演者 河田則文(大阪市立大学大学院医学研究科肝胆膵病態内科学)
抄録 Aim : Cytoglobin (Cygb) is a recently discovered vertebrate gtobin withunknow-n function. To study the biological function of Cygb in vivowegenerated Cygb knockout mice and investigated their susceptibility to NN-diethylnitrosamine (DEN) 一induced turnorigenesis. Methods : Micelackng exon 1 of the Cygb gene were generated using the lox-P system.Four-week-old’Cygb” ’ (wi’ld-type)Cygb ”’ (heterozygote)and Cygb’ ’(homozygote) male mice were administrated DEN in drinking water atthe dose of 25 pp1n for 25 weeks or O.05 ppm for 36 weeksTumor forma-tion and the role Qf Cygb in DEN-mediated carcinogenesis were ana-Iyzed. Results : Cygb deficiency prometed the DEN-induced deveEop-rnent of liver and lung tumors. All Cygb.. and Cygb”. mice treated wi出as ppm DEN exhibited liver tumorscompared with 44.4% of their wild-type coun’terparts. Lung tumors were present only in Cygb-deficientmice. More than 40% of Cygb ” mice developed liver and iung tumorgatthe non-toxic dose of DEN(OP5 ppm)wbich did not induce tu皿ors inwild-type miceCygb loss was associated with increased cancer ce皿pr(ンliferation. elevated Erk and Akt activationover-expression of tumor pro-moting cytokineshepatic collagen accumulationand increased oxidativestress. Conelusions : This study is the first to report that Cygb deficiencyinduced susceptibility te cancer development in the liver as well as thelungs of mice under DEN treatment Cygb-deficient mice can be a usefulanimal rnodel to study liver and lungs tumorigenesis. Globins such asCygb wM thus shed new light on the biology of organ carcinogenesis
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