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KMID : 0620920080400030345
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Experimental & Molecular Medicine
2008 Volume.40 No. 3 p.345 ~ p.353
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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
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Yun Hye-Jin
Cho Young-Hwa
Moon Young-Sun
Park Young-Woo
Yoon Hye-Kyoung
Kim Yeun-Ju
Cho Sung-Ha
Lee Young-Ill
Kang Bong-Su
Kim Wun-Jae
Park Kee-Rang
Seol Won-Gi
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Abstract
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For cancer gene therapy, cancer-specific overexpression 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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KEYWORD
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breast neoplasms, gene therapy, PRC1 protein, human, ribonucleotide reductase M2
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