Critical role of CDK2 for melanoma growth linked to its melanocyte-specific transcriptional regulation by MITF.
Cancer Cell
; 6(6): 565-76, 2004 Dec.
Article
em En
| MEDLINE
| ID: mdl-15607961
ABSTRACT
The genomic organization of the CDK2 gene, which overlaps the melanocyte-specific gene SILV/PMEL17, poses an interesting regulatory challenge. We show that, despite its ubiquitous expression, CDK2 exhibits tissue-specific regulation by the essential melanocyte lineage transcription factor MITF. In addition, functional studies revealed this regulation to be critical for maintaining CDK2 kinase activity and growth of melanoma cells. Expression levels of MITF and CDK2 are tightly correlated in primary melanoma specimens and predict susceptibility to the CDK2 inhibitor roscovitine. CDK2 depletion suppressed growth and cell cycle progression in melanoma, but not other cancers, corroborating previous results. Collectively, these data indicate that CDK2 activity in melanoma is largely maintained at the transcriptional level by MITF, and unlike other malignancies, it may be a suitable drug target in melanoma.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Quinases relacionadas a CDC2 e CDC28
/
Proteínas de Ligação a DNA
/
Melanoma
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos