Control of gene therapy by MDR1 and EGR1 promoter sequences in transcriptional targeting by chemotherapy (Review).
The promising benefits of cancer gene therapy have been limited by the inability to deliver therapeutic genes homogeneously throughout the tumor mass and to control gene expression within the tumor cells. Transcriptional targeting, the use of DNA regulatory promoter sequences to localize transgene expression, has been employed as a solution to circumvent these limitations. TNF-alpha is a cytokine that exhibits potent anticancer properties, but its utility following systemic administration is limited by toxicity. We review a strategy whereby ligating TNF-alpha to segments of the chemo-inducible EGR1 or MDR1 promoters activates expression of TNF-alpha cDNA and enhances effectiveness of gene therapy and chemotherapy.
Lopez
Carlos A
CA
Department of Surgery, University of Chicago, Chicago, IL 60637, USA.
Park
James O
JO
Mauceri
Helena J
HJ
Beckett
Michael A
MA
Weichselbaum
Ralph R
RR
Posner
Mitchell C
MC
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D002986:Clinical Trials as Topic; D003603:Cytotoxins; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D011839:Radiation, Ionizing; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003603:Cytotoxins; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D004247:DNA