Document Detail


Restoration of CDKN2A into melanoma cells induces morphologic changes and reduction in growth rate but not anchorage-independent growth reversal.
MedLine Citation:
PMID:  9204956     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CDKN2A is a melanoma susceptibility gene that is mutated and/or deleted in familial and sporadic melanoma as well as in a range of other tumors. It encodes a cell cycle regulator, p16, whose function is to inhibit activity of cyclin-dependent kinases 4 and 6. We set out to investigate the effect of reintroducing CDKN2A into MM96L, a melanoma cell line that does not express p16, by electroporation of wt CDKN2A cDNA. Our results show that transfection of the CDKN2A cDNA has a dramatic effect on cell morphology, inducing a more dendritic phenotype resembling that of adult melanocytes. This effect on cell morphology was not cell line specific because it was reproduced in another melanoma line (SK-MEL-13), which has a homozygous deletion of CDKN2A. It was abolished by mutations that abrogate p16 function, as shown by transfection of a Pro81Leu p16 variant. Reintroduction of levels of p16 protein similar to those of cultured neonatal foreskin melanocytes decreased the growth rate of the transfected clones. Surprisingly, we did not see any effect on anchorage-independent growth or on the following melanoma markers tested by western blotting: p21/WAF1, tyrosinase-related antigen 1, HMB45, and intermediate filament antigen. These data indicate that reintroduction into melanoma cells of wild type p16 at levels similar to cultured melanocytes can induce morphologic changes and suppress growth but is not sufficient to affect anchorage-independent growth.
Authors:
M Castellano; B G Gabrielli; C J Hussussian; N C Dracopoli; N K Hayward
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  109     ISSN:  0022-202X     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  1997 Jul 
Date Detail:
Created Date:  1997-07-17     Completed Date:  1997-07-17     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  61-8     Citation Subset:  IM    
Affiliation:
Joint Experimental Oncology Program, Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Herston, Australia.
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MeSH Terms
Descriptor/Qualifier:
Aged
Carrier Proteins / genetics*
Clone Cells / metabolism
Cyclin-Dependent Kinase Inhibitor p16
Enzyme Inhibitors / pharmacology
Female
Gene Expression
Genes, Tumor Suppressor
Genetic Variation
Humans
Melanoma / genetics,  pathology
Protein Kinase Inhibitors
Transfection
Tumor Cells, Cultured / drug effects
Tumor Markers, Biological / analysis
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Enzyme Inhibitors; 0/Protein Kinase Inhibitors; 0/Tumor Markers, Biological

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