2003, English, Article edition: p16/Cyclin-Dependent Kinase Inhibitor 2A Deficiency in Human Melanocyte Senescence, Apoptosis, and Immortalization: Possible Implications for Melanoma Progression Sviderskaya, Elena V.; Gray-Schopfer, Vanessa C.; Hill, Simon P.; ...

User activity

Share to:
 
Bookmark: http://trove.nla.gov.au/version/209815
Physical Description
  • text/​html
Published
  • Oxford University Press
  • 2003-05-21 00:00:00.0
Language
  • English

Edition details

Title
  • p16/​Cyclin-Dependent Kinase Inhibitor 2A Deficiency in Human Melanocyte Senescence, Apoptosis, and Immortalization: Possible Implications for Melanoma Progression
Author
  • Sviderskaya, Elena V.
  • Gray-Schopfer, Vanessa C.
  • Hill, Simon P.
  • Smit, Nico P.
  • Evans-Whipp, Tracy J.
  • Bond, Jane
  • Hill, Lucy
  • Bataille, Veronique
  • Peters, Gordon
  • Kipling, David
  • Wynford-Thomas, David
  • Bennett, Dorothy C.
Published
  • Oxford University Press
  • 2003-05-21 00:00:00.0
Physical Description
  • text/​html
Subjects
Notes
  • Background: The melanoma susceptibility locus cyclin-dependent kinase inhibitor 2A encodes two unrelated cell growth inhibitors, p16 and alternative reading frame (ARF). In fibroblasts, both proteins are implicated in cellular senescence, a key barrier to tumor development. The p16 coding sequence is more often mutated in melanoma families than is the ARF sequence. To investigate the role of p16 in melanocytes, we assessed aspects of growth, apoptosis, and immortalization in melanocytes cultured from two melanoma patients, both of whom had two inactive p16 alleles but functional ARF. Methods: Growth and senescence were evaluated by cumulative population-doubling curves, and apoptosis by terminal deoxytransferase labeling. Expression of p53 and p21, which are associated with fibroblast senescence, was assessed by immunoblotting. Amphotropic retroviruses were used to transfer exogenous gene sequences into the melanocytes. Results: Both melanocyte cultures showed high rates of apoptosis, which were reduced when the cells were grown in the presence of keratinocyte feeder cells or human stem cell factor plus endothelin 1. With these growth factors, both cultures proliferated for 45–55 net population doublings, markedly longer than the maximum of 10 net population doublings of normal adult human melanocytes in similar media, indicating impaired senescence. One of the cultures developed chromosomal aberrations, with numerous dicentric chromosomes at senescence, consistent with telomere dysfunction. p53 and p21 levels were not elevated in senescent normal melanocytes but were elevated in senescent p16-deficient melanocytes. Interference with p53 function by transfer of human papillomavirus 16-E6 further extended the lifespan of p16-deficient melanocytes. Human telomerase reverse transcriptase was sufficient to immortalize both these cell strains but not normal melanocytes. Conclusion: Normal senescence in human melanocytes requires p16 activity. p53 contributes to a delayed form of senescence that requires telomere shortening, in p16-deficient melanocytes. These findings provide some basis for the role of p16 in melanoma susceptibility.
Terms of Use
  • Copyright (C) 2003, The Oxford University Press
Language
  • English
Contributed by
OAIster

Get this edition

  • Set up My libraries

    How do I set up "My libraries"?

    In order to set up a list of libraries that you have access to, you must first login or sign up. Then set up a personal list of libraries from your profile page by clicking on your user name at the top right of any screen.

  • All (1)
  • Unknown (1)
None of your libraries hold this item.
None of your libraries hold this item.
None of your libraries hold this item.
None of your libraries hold this item.
None of your libraries hold this item.
None of your libraries hold this item.
None of your libraries hold this item.
None of your libraries hold this item.

User activity


e.g. test cricket, Perth (WA), "Parkes, Henry"

Separate different tags with a comma. To include a comma in your tag, surround the tag with double quotes.

Be the first to add a tag for this edition

Be the first to add this to a list

Comments and reviews

What are comments? Add a comment

No user comments or reviews for this version

Add a comment