Restoration of CDKN2A into melanoma cells induces morphologic changes and reduction in growth rate but not anchorage-independent growth reversal

Castellano, M, Gabrielli, BG, Hussussian, CJ, Dracopoli, NC and Hayward, NK (1997) Restoration of CDKN2A into melanoma cells induces morphologic changes and reduction in growth rate but not anchorage-independent growth reversal. Journal of Investigative Dermatology, 109 1: 61-68. doi:10.1111/1523-1747.ep12276538


Author Castellano, M
Gabrielli, BG
Hussussian, CJ
Dracopoli, NC
Hayward, NK
Title Restoration of CDKN2A into melanoma cells induces morphologic changes and reduction in growth rate but not anchorage-independent growth reversal
Journal name Journal of Investigative Dermatology   Check publisher's open access policy
ISSN 0022-202X
Publication date 1997-07-01
Year available 1997
Sub-type Article (original research)
DOI 10.1111/1523-1747.ep12276538
Open Access Status
Volume 109
Issue 1
Start page 61
End page 68
Total pages 8
Place of publication MALDEN
Publisher BLACKWELL SCIENCE INC
Language eng
Abstract 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 p 16, 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.
Keyword p16
transfection
melanoma-associated markers
Tumor-Suppressor Gene
Familial Melanoma
Human Cancers
Retinoblastoma-Protein
Cyclin D1
Rb Gene
P16(Ink4)
P16
Inhibition
Expression
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: ResearcherID Downloads - Archived
 
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