Critical role of CDK2 for melanoma growth linked to its melanocyte-specific transcriptional regulation by MITF.
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Critical role of CDK2 for melanoma growth linked to its melanocyte-specific transcriptional regulation by MITF. / Du, Jinyan; Widlund, Hans R; Horstmann, Martin; Ramaswamy, Sridhar; Ross, Ken; Huber, Wade E; Nishimura, Emi K; Golub, Todd R; Fisher, David E.
in: CANCER CELL, Jahrgang 6, Nr. 6, 6, 2004, S. 565-576.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Critical role of CDK2 for melanoma growth linked to its melanocyte-specific transcriptional regulation by MITF.
AU - Du, Jinyan
AU - Widlund, Hans R
AU - Horstmann, Martin
AU - Ramaswamy, Sridhar
AU - Ross, Ken
AU - Huber, Wade E
AU - Nishimura, Emi K
AU - Golub, Todd R
AU - Fisher, David E
PY - 2004
Y1 - 2004
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 6
SP - 565
EP - 576
JO - CANCER CELL
JF - CANCER CELL
SN - 1535-6108
IS - 6
M1 - 6
ER -
