GenomeRNAi - a database for RNAi phenotypes and reagents
TitleScreen TitleAssayBiomodelSpecies
Identification of CDK10 as an important determinant of resistance to endocrine therapy for breast cancer. Iorns et al. (2008) Combinatorial effect with 4OH tamoxifen ViabilityMCF7H. sapiens


Therapies that target estrogen signaling have transformed the treatment of breast cancer. However, the effectiveness of these agents is limited by the development of resistance. Here, an RNAi screen was used to identify modifiers of tamoxifen sensitivity. We demonstrate that CDK10 is an important determinant of resistance to endocrine therapies and show that CDK10 silencing increases ETS2-driven transcription of c-RAF, resulting in MAPK pathway activation and loss of tumor cell reliance upon estrogen signaling. Patients with ER alpha-positive tumors that express low levels of CDK10 relapse early on tamoxifen, demonstrating the clinical significance of these observations. The association of low levels of CDK10 with methylation of the CDK10 promoter suggests a mechanism by which CDK10 expression is reduced in tumors.

Screen details

Stable Id: GR00200-A
Screen title: Combinatorial effect with 4OH tamoxifen
Assay: Viability
Method: Luminescence
Scope: Kinases
Screen type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: MCF7
Library: Dharmacon, siARRAY
Reagent type: siRNA
Score type: Z-score
Cutoff: >= 3