Reference Detail

Ref Type

Journal Article

PMID

(15767545)

Authors

Atienza JM, Roth RB, Rosette C, Smylie KJ, Kammerer S, Rehbock J, Ekblom J, Denissenko MF

Title

Suppression of RAD21 gene expression decreases cell growth and enhances cytotoxicity of etoposide and bleomycin in human breast cancer cells.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Molecular cancer therapeutics	4	3	2005 Mar	361-8	Mol Cancer Ther

URL

Abstract Text

A genome-wide case-control association study done in our laboratory has identified a single nucleotide polymorphism located in RAD21 as being significantly associated with breast cancer susceptibility. RAD21 is believed to function in sister chromatid alignment as part of the cohesin complex and also in double-strand break (DSB) repair. Following our initial finding, expression studies revealed a 1.25- to 2.5-fold increased expression of this gene in several human breast cancer cell lines as compared with normal breast tissue. To determine whether suppression of RAD21 expression influences cellular proliferation, RNA interference technology was used in breast cancer cell lines MCF-7 and T-47D. Proliferation of cells treated with RAD21-specific small inhibitory RNA (siRNA) was significantly reduced as compared with mock-transfected cells and cells transfected with a control siRNA (Lamin A/C). This inhibition of proliferation correlated with a significant reduction in the expression of RAD21 mRNA and with an increased level of apoptosis. Moreover, MCF-7 cell sensitivity to two DNA-damaging chemotherapeutic agents, etoposide and bleomycin, was increased after inhibition of RAD21 expression with a dose reduction factor 50 (DRF50) of 1.42 and 3.71, respectively. At the highest concentrations of etoposide and bleomycin administered, cells transfected with a single siRNA duplex targeted against RAD21 showed 57% and 60% survival as compared with control cells, respectively. Based on these findings, we conclude that RAD21 is a novel target for developing cancer therapeutics that can potentially enhance the antitumor activity of chemotherapeutic agents acting via induction of DNA damage.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References