Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1993-6-29
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1407-13
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:8389027-Blotting, Northern, pubmed-meshheading:8389027-Breast, pubmed-meshheading:8389027-Cell Aging, pubmed-meshheading:8389027-Cell Line, Transformed, pubmed-meshheading:8389027-Cell Transformation, Viral, pubmed-meshheading:8389027-Epithelium, pubmed-meshheading:8389027-Female, pubmed-meshheading:8389027-Fibroblasts, pubmed-meshheading:8389027-Humans, pubmed-meshheading:8389027-Kinetics, pubmed-meshheading:8389027-Oncogene Proteins, Viral, pubmed-meshheading:8389027-Papillomaviridae, pubmed-meshheading:8389027-Plasmids, pubmed-meshheading:8389027-Promoter Regions, Genetic, pubmed-meshheading:8389027-RNA, Messenger, pubmed-meshheading:8389027-Repressor Proteins, pubmed-meshheading:8389027-Simian virus 40, pubmed-meshheading:8389027-Telomere, pubmed-meshheading:8389027-Time Factors, pubmed-meshheading:8389027-Transfection
pubmed:year
1993
pubmed:articleTitle
E6 of human papillomavirus type 16 can overcome the M1 stage of immortalization in human mammary epithelial cells but not in human fibroblasts.
pubmed:affiliation
University of Texas Southwestern Medical Center, Department of Cell Biology and Neurosciences, Dallas 75235-9039.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't