title: Transcriptional targeting of gene expression in breast cancer by the promoters of protein regulator of cytokinesis 1 and ribonuclease reductase 2.
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.
authors.affiliation: Institute for Brain Science and Technology, Inje University, Busan, Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Yun
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Cho
authors.forename: Youngsun
authors.initials: Y
authors.lastname: Moon
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Park
authors.forename: Hye-Kyoung
authors.initials: HK
authors.lastname: Yoon
authors.forename: Yeun-Ju
authors.initials: YJ
authors.lastname: Kim
authors.forename: Sung-Ha
authors.initials: SH
authors.lastname: Cho
authors.forename: Young-Ill
authors.initials: YI
authors.lastname: Lee
authors.forename: Bong-Su
authors.initials: BS
authors.lastname: Kang
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Keerang
authors.initials: K
authors.lastname: Park
authors.forename: Wongi
authors.initials: W
authors.lastname: Seo
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000628:therapy; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D003587:Cytomegalovirus; D000229:Dependovirus; D005260:Female; D018390:Gene Targeting; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012262:Ribonucleoside Diphosphate Reductase / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D018797:Cell Cycle Proteins; C116662:PRC1 protein, human; D049452:Green Fluorescent Proteins; C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase