Multiple abnormalities of the p16(INK4a)-pRb regulatory pathway in cultured melanoma cells

H. Rizos*, A. P. Darmanian, J. O. Indsto, J. A. Shannon, R. F. Kefford, G. J. Mann

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

The retinoblastoma protein (pRb) pathway is critical in regulating the G1 phase of the cell cycle and it is frequently disrupted in human cancers. Components of the pRb pathway which are often altered in tumour progression include the INK4 cyclin-dependent kinase (CDK) inhibitors p16(INK4a)/CDKN2A and p15(INK4b)/CDKN2B, CDK4, D-type cyclins and pRb. Several of these components were studied in a series of cultured melanoma cell lines in order to determine the frequency and spectrum of genetic alterations and to define targets for potential gene transfer studies. Also studied were the p16(INK4a) alternate transcript (p14ARF) and the p21(waf1) CDK inhibitor. The majority of the melanoma cell lines tested (13 out of 17; 76%) carried mutated (two), deleted (nine) or silenced (two) p16(INK4a). CDK4 was mutated or overexpressed in two melanoma cell lines with homozygously deleted CDKN2A and CDKN2B genes. This suggests that the selective growth advantages afforded by CDKN2A inactivation and CDK4 insensitivity are distinct and may involve the mediation of other CDK inhibitors or CDKs.

Original languageEnglish
Pages (from-to)10-19
Number of pages10
JournalMelanoma Research
Volume9
Issue number1
Publication statusPublished - 1999
Externally publishedYes

Keywords

  • CDK4 gene
  • CDKN2A gene
  • Cell cycle
  • Melanoma cells
  • Retinoblastoma protein

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