Document Detail


c-Myc induction of programmed cell death may contribute to carcinogenesis: a perspective inspired by several concepts of chemical carcinogenesis.
MedLine Citation:
PMID:  21278493     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The c-Myc protein, encoded by c-myc gene, in its wild-type form can induce tumors with a high frequency and can induce massive programmed cell death (PCD) in most transgenic mouse models, with greater efficiency than other oncogenes. Evidence also indicates that c-Myc can cause proliferative inhibition, i.e. mitoinhibition. The c-Myc-induced PCD and mitoinhibition, which may be attributable to its inhibition of cyclin D1 and induction of p53, may impose a pressure of compensatory proliferation, i.e. regeneration, onto the initiated cells (cancer progenitor cells) that occur sporadically and are resistant to the mitoinhibition. The initiated cells can thus proliferate robustly and progress to a malignancy. This hypothetical thinking, i.e. the concurrent PCD and mitoinhibition induced by c-Myc can promote carcinogenesis, predicts that an optimal balance is achieved between cell death and ensuing regeneration during oncogenic transformation by c-Myc, which can better promote carcinogenesis. In this perspective, we summarize accumulating evidence and challenge the current model that oncoprotein induces carcinogenesis by promoting cellular proliferation and/or inhibiting PCD. Inspired by c-myc oncogene, we surmise that many tumor-suppressive or growth-inhibitory genes may also be able to promote carcinogenesis in a similar way, i.e. by inducing PCD and/or mitoinhibition of normal cells to create a need for compensatory proliferation that drives a robust replication of initiating cells.
Authors:
Chenguang Wang; Yanhong Tai; Michael P Lisanti; D Joshua Liao
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2011-04-01
Journal Detail:
Title:  Cancer biology & therapy     Volume:  11     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-04     Completed Date:  2011-07-19     Revised Date:  2011-07-28    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  615-26     Citation Subset:  IM    
Affiliation:
Department of Stem Cell and Regenerative Medicine, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified
Apoptosis / genetics*
Apoptosis Regulatory Proteins / metabolism
Cell Proliferation
Cell Transformation, Neoplastic / chemically induced*,  genetics*
Cyclin D / antagonists & inhibitors,  metabolism
Humans
Oncogene Proteins / antagonists & inhibitors
Proto-Oncogene Proteins c-myc / genetics*,  metabolism*
Tumor Suppressor Protein p53 / metabolism
Grant Support
ID/Acronym/Agency:
R01 CA100864/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Cyclin D; 0/Oncogene Proteins; 0/Proto-Oncogene Proteins c-myc; 0/Tumor Suppressor Protein p53
Comments/Corrections

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