Development of a cancer-targeted tissue-specific promoter system.
Present cancer gene therapy using proapoptotic genes has had limited success because the therapy is prone to cause side effects as a result of the lack of tissue and cancer specificity. To target cancer cells without damaging normal cells, we have designed a novel dual promoter system in which a tissue-specific transcription system under the control of a cancer-specific promoter drives expression of a therapeutic gene. The applicability of this system was demonstrated by adapting it to target lung cancer. We termed this lung cancer system TTS (TTF1 gene under the control of human telomerase reverse transcriptase promoter and human surfactant protein A1 promoter). The TTS system showed much higher promoter activity in lung cancer cells compared with other kinds of cancer and normal lung cells, including stem cells. Moreover, insertion of negative glucocorticoid responsive elements in the system allows it to be drug controllable. The approaches that we have used could be adapted to target other types of cancer. We report a novel cancer-targeted tissue-specific dual promoter system designed for gene therapy.
Fukazawa
Takuya
T
Department of Biomedical Sciences, University of California, Riverside, California, USA. FukazawaT@aol.com
Maeda
Yutaka
Y
Sladek
Frances M
FM
Owen-Schaub
Laurie B
LB
D018287:Carcinoma, Large Cell; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008175:Lung Neoplasms; D011401:Promoter Regions, Genetic / Q000235:genetics*; D019098:Telomerase / Q000235:genetics; D014157:Transcription Factors; D014162:Transfection
D004268:DNA-Binding Proteins; C504003:TTF1 protein, human; D014157:Transcription Factors; D003907:Dexamethasone; D008156:Luciferases; D019098:Telomerase