Transcriptional targeting of gene expression in breast cancer by the promoters of protein regulator of cytokinesis 1 and ribonuclease reductase 2.
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.
Yun
Hye Jin
HJ
Institute for Brain Science and Technology, Inje University, Busan, Korea.
Cho
Young-Hwa
YH
Moon
Youngsun
Y
Park
Young Woo
YW
Yoon
Hye-Kyoung
HK
Kim
Yeun-Ju
YJ
Cho
Sung-Ha
SH
Lee
Young-Ill
YI
Kang
Bong-Su
BS
Kim
Wun-Jae
WJ
Park
Keerang
K
Seo
Wongi
W
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
D018797:Cell Cycle Proteins; C116662:PRC1 protein, human; D049452:Green Fluorescent Proteins; C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase