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Transcriptional targeting of gene expression in breast cancer by the promoters of protein regulator of cytokinesis 1 and ribonuclease reductase 2
Experimental & Molecular Medicine ; : 345-353, 2008.
Article in English | WPRIM | ID: wpr-205421
ABSTRACT
For cancer gene therapy, cancer-specific over-expression of a therapeutic gene is required to reduce side effects derived from expression of the gene in normal cells. To develop such an expression vector, we searched for genes over-expressed and/or specifically expressed in cancer cells using bioinformatics and have selected genes coding for protein regulator of cytokinesis 1 (PRC1) and ribonuclease reductase 2 (RRM2) as candidates. Their cancer-specific expressions were confirmed in both breast cancer cell lines and patient tissues. We compared each promoter's cancer-specific activity in the breast normal and cancer cell lines using the luciferase gene as a reporter and confirmed cancer-specific expression of both PRC1 and RRM2 promoters. To test activities of these promoters in viral vectors, the promoters were also cloned into an adeno-associated viral (AAV) vector containing green fluorescence protein (GFP) as the reporter. The GFP expression levels by these promoters were various depending on cell lines tested and, in MDA-MB-231 cells, GFP activities derived from the PRC1 and RRM2 promoters were as strong as that from the cytomegalovirus (CMV) promoter. Our result showed that a vector containing the PRC1 or RRM2 promoter could be used for breast cancer specific overexpression in gene therapy.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Ribonucleoside Diphosphate Reductase / Breast Neoplasms / Genetic Therapy / Transcriptional Activation / Promoter Regions, Genetic / Cloning, Molecular / Dependovirus / Gene Targeting / Cell Cycle Proteins / Cytomegalovirus Limits: Female / Humans Language: English Journal: Experimental & Molecular Medicine Year: 2008 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Ribonucleoside Diphosphate Reductase / Breast Neoplasms / Genetic Therapy / Transcriptional Activation / Promoter Regions, Genetic / Cloning, Molecular / Dependovirus / Gene Targeting / Cell Cycle Proteins / Cytomegalovirus Limits: Female / Humans Language: English Journal: Experimental & Molecular Medicine Year: 2008 Type: Article