Exp Mol Med.  2008 Jun;40(3):345-353. 10.3858/emm.2008.40.3.345.

Transcriptional targeting of gene expression in breast cancer by the promoters of protein regulator of cytokinesis 1 and ribonuclease reductase 2

• Yun HJ
• Cho YH
• Moon Y
• Park YW
• Yoon HK
• Kim YJ
• Cho SH
• Lee YI
• Kang BS
• Kim WJ
• Park K
• Seo W

• KMID: 756337
• DOI: http://doi.org/10.3858/emm.2008.40.3.345

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.

Keyword

breast neoplasms; gene therapy; PRC1 protein, human; ribonucleotide reductase M2

MeSH Terms

Breast Neoplasms/*genetics/therapy
Cell Cycle Proteins/*genetics/metabolism
Cell Line, Tumor
Cloning, Molecular
Cytomegalovirus
Dependovirus
Female
*Gene Targeting
Gene Therapy
Genetic Vectors
Green Fluorescent Proteins
Humans
Promoter Regions, Genetic/*genetics
Ribonucleoside Diphosphate Reductase/*genetics/metabolism
*Transcriptional Activation