|Transgenic human programmed cell death 5 expression in mice suppresses skin cancer development by enhancing apoptosis|
|Li, Yanhui1; Zhou, Gang2; La, Lijun1; Chi, Xiaochun1; Cao, Ye1; Liu, Jing1; Zhang, Zhanhui1; Chen, Yingyu3; Wu, Baiyan1|
|关键词||PDCD5 Transgenic mice Apoptosis Tumor suppressor gene Cancer therapy|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, Research & Experimental ; Pharmacology & Pharmacy|
|研究领域[WOS]||Research & Experimental Medicine ; Pharmacology & Pharmacy|
|关键词[WOS]||RADIATION-INDUCED APOPTOSIS ; PDCD5 ; P53 ; OVEREXPRESSION ; TRANSCRIPTOME ; RADIOTHERAPY ; PROFILES ; LEUKEMIA ; TFAR19|
Aims: We sought to probe the role of human programmed cell death 5 (PDCD5) in vivo and to understand its mechanisms.
Main methods: A transgenic mouse model of human PDCD5 was generated by pronuclear microinjection. Apoptosis in tissues of three independent transgenic mouse lines was quantified by terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling (TUNEL) and compared to wild type littermates. Their lifespan was compared. 8-Week PDCD5 mice and wild type mice (at a group of 5) were treated with carcinogen 3-methylcholanthrene (3-MC) at 5 mu g per week to induce skin cancer. Cancer development was measured by examining hematoxylin and eosin (H&E) stained skin sections after 5 weeks and 10 weeks treatment. Protein expression was determined by Western blot and apoptosis of skin cells was quantified by TUNEL.
Key findings: Starting from 5 months after birth, significant autonomous apoptosis was observed in multiple tissues of transgenic mice including skin, liver, spleen, adrenal gland and thyroid gland comparing to their wild type littermates. The average lifespan of PDCD5 mice was reduced to 9.75 months (normally 24-30 months). Moreover, carcinogen 3-MC induced skin cancer development was attenuated in the lesion of PDCD5 transgenic mice by enhancing apoptosis. Pro-apoptotic protein Bax expression was up-regulated in the 3-MC treated skin of transgenic mice.
Significance: These results suggest PDCD5 plays an antitumor role by enhancing apoptosis in animal physiological settings. Therefore, PDCD5 is a potential target for cancer therapy. (C) 2013 Elsevier Inc. All rights reserved.
|项目编号||2011CB910103 ; 30871263|
|资助机构||National Key Project for Basic Research of China (973) ; National Natural Science Foundation of China|
|作者单位||1.Peking Univ, Hlth Sci Ctr, Dept Med Genet, Sch Basic Sci, Beijing 100191, Peoples R China|
2.Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44106 USA
3.Peking Univ, Hlth Sci Ctr, Dept Immunol, Sch Basic Sci, Beijing 100191, Peoples R China
|Li, Yanhui,Zhou, Gang,La, Lijun,et al. Transgenic human programmed cell death 5 expression in mice suppresses skin cancer development by enhancing apoptosis[J]. LIFE SCIENCES,2013,92(24-26):1208-1214.|
|APA||Li, Yanhui.,Zhou, Gang.,La, Lijun.,Chi, Xiaochun.,Cao, Ye.,...&Wu, Baiyan.(2013).Transgenic human programmed cell death 5 expression in mice suppresses skin cancer development by enhancing apoptosis.LIFE SCIENCES,92(24-26),1208-1214.|
|MLA||Li, Yanhui,et al."Transgenic human programmed cell death 5 expression in mice suppresses skin cancer development by enhancing apoptosis".LIFE SCIENCES 92.24-26(2013):1208-1214.|
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