Transcriptional targeting of gene expression in breast cancer by the promoters of protein regulator of cytokinesis 1 and ribonuclease reductase 2.
10.3858/emm.2008.40.3.345
- Author:
Hye Jin YUN
1
;
Young Hwa CHO
;
Youngsun MOON
;
Young Woo PARK
;
Hye Kyoung YOON
;
Yeun Ju KIM
;
Sung Ha CHO
;
Young Ill LEE
;
Bong Su KANG
;
Wun Jae KIM
;
Keerang PARK
;
Wongi SEO
Author Information
1. Institute for Brain Science and Technology, Inje University , Busan 614-735, Korea. wseol@inje.ac.kr
- Publication Type:Original Article ; Comparative Study ; Research Support, Non-U.S. Gov't
- Keywords:
breast neoplasms;
gene therapy;
PRC1 protein, human;
ribonucleotide reductase M2
- MeSH:
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
- From:Experimental & Molecular Medicine
2008;40(3):345-353
- CountryRepublic of Korea
- Language:English
-
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.
