Document Detail


E6 of human papillomavirus type 16 can overcome the M1 stage of immortalization in human mammary epithelial cells but not in human fibroblasts.
MedLine Citation:
PMID:  8389027     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Immortalization is the consequence of the inactivation or bypass of two mortality stage mechanisms, M1 and M2, which are controlled by several genes including Rb and p53 in human fibroblasts. Abrogation of the M1 controls can be obtained through the activity of DNA tumor virus genes such as E6 and E7 of human papillomavirus 16 (HPV16). Fibroblasts expressing both E6 (which binds p53) and E7 (which binds Rb) bypass M1 and continue replicating (exhibit an extended lifespan) until an independent mechanism, M2, is activated. The inactivation of the M2 mechanism finally results in cell immortalization. The present study establishes a difference in the tissue-specific mechanisms for the control of the M1 stage of cellular senescence. The expression of HPV16 E6 was sufficient to bypass the M1 stage of cellular senescence and confer an extended lifespan in human mammary epithelial cells but not in fibroblasts. This implies that the M1 mechanism in human mammary epithelial cells does not involve the constitutive activation of Rb function as it does in fibroblasts. In addition, the results confirmed that the expression of HPV16 E6 (or both E6 and E7) did not directly immortalize the human mammary epithelial cells, since the inactivation of a second event, M2, was required to achieve immortalization. These observations are considered in the context of the telomere shortening model of cellular senescence.
Authors:
J W Shay; W E Wright; D Brasiskyte; B A Van der Haegen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  8     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1993 Jun 
Date Detail:
Created Date:  1993-06-29     Completed Date:  1993-06-29     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1407-13     Citation Subset:  IM    
Affiliation:
University of Texas Southwestern Medical Center, Department of Cell Biology and Neurosciences, Dallas 75235-9039.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Northern
Breast
Cell Aging
Cell Line, Transformed
Cell Transformation, Viral*
Epithelium
Female
Fibroblasts
Humans
Kinetics
Oncogene Proteins, Viral / genetics*,  metabolism
Papillomaviridae / genetics*
Plasmids
Promoter Regions, Genetic
RNA, Messenger / metabolism
Repressor Proteins*
Simian virus 40 / genetics
Telomere / physiology
Time Factors
Transfection
Grant Support
ID/Acronym/Agency:
AG07992/AG/NIA NIH HHS; CA50195/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/E6 protein, Human papillomavirus type 16; 0/Oncogene Proteins, Viral; 0/RNA, Messenger; 0/Repressor Proteins

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