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Rewiring drug-activated p53-regulatory network from suppressing to promoting tumorigenesis
Wei Song1; Wang Jiguang1; Ying Yang1; Jing Naihe1; Xiangsun Zhang2; Chen Luonan1; Wu Jiarui1
2012
Source PublicationJournal of Molecular Cell Biology
ISSN1674-2788
Volume4Issue:4Pages:197
AbstractMany of oncogenes and tumor suppressor genes have been found to exert variable and even opposing roles in different kinds of tumors or at different stages of cancer development. Here we showed that tumorigenic potential of mouse embryonic carcinoma P19 cells cultured in adherent plates (attached-P19-cells) was suppressed by a chemotherapeutic agent, 5-aza-2-deoxycytidine (ZdCyd), whereas the higher pro-tumorigenicity of P19 cells growing in suspension (detached-P19-cells) was generated by the ZdCyd treatment. Surprisingly, p53 activity was highly up-regulated by ZdCyd in both growing conditions. By our developed computational approaches, we revealed that there was a significant enrichment of apoptotic pathways in the ZdCyd-induced p53-dominant gene-regulatory network in attached P19 cells, whereas the pro-survival genes were significantly enriched in the ZdCyd-induced p53 network in detached P19 cells. The proteinprotein interaction network of the ZdCyd-treated detached P19 cells was significantly different from that of ZdCyd-treated attached P19 cells. On the other hand, inhibition of p53 expression by siRNA suppressed the ZdCyd-induced tumorigenesis of detached P19 cells, suggesting that the ZdCyd-activated p53 plays oncogenic function in detached P19 cells. Taken together, these results indicate a context-dependent role for the ZdCyd-activated p53-dominant network in tumorigenesis.
Language英语
Funding Project[Ministry of Science and Technology] ; [National Natural Science Foundation of China]
Document Type期刊论文
Identifierhttp://ir.amss.ac.cn/handle/2S8OKBNM/42347
Collection应用数学研究所
Affiliation1.中国科学院上海生命科学研究院
2.中国科学院数学与系统科学研究院
Recommended Citation
GB/T 7714
Wei Song,Wang Jiguang,Ying Yang,et al. Rewiring drug-activated p53-regulatory network from suppressing to promoting tumorigenesis[J]. Journal of Molecular Cell Biology,2012,4(4):197.
APA Wei Song.,Wang Jiguang.,Ying Yang.,Jing Naihe.,Xiangsun Zhang.,...&Wu Jiarui.(2012).Rewiring drug-activated p53-regulatory network from suppressing to promoting tumorigenesis.Journal of Molecular Cell Biology,4(4),197.
MLA Wei Song,et al."Rewiring drug-activated p53-regulatory network from suppressing to promoting tumorigenesis".Journal of Molecular Cell Biology 4.4(2012):197.
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