Modulation of estrogen receptor gene transcription in breast cancer cells by liposome delivered decoy molecules.
It is well known that breast carcinomas without estrogen receptor (ER) have a poor prognosis and do not respond to antiestrogenic therapy. In analyzing the question of the lack of ER gene expression, we have considered the possibility to modify the ER gene expression by transfecting ER-negative breast cancer cells with a polymerase chain reaction product mimicking a putative negative regulatory region (--3258/--3157) inside the P3 ER gene promoter. Here we have demonstrated the efficacy of the selected sequence used as a decoy molecule in restoring the ER gene transcription. When this DNA was complexed and delivered by cationic liposomes (PC:DOTAP) a significant increase in the decoy effect was obtained. Breast cancer cells receiving the combination treatment responded substantially better to reactivation of quiescent ER gene than cells that had received DNA with calcium phosphate. This information may be useful for a series of in vitro transfections and also for in vivo application of the decoy strategy that is a potential therapeutic tool to control disease-related genes such as ER gene in breast cancer.
Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Via Luigi Borsari, 46 44100 Ferrara, Italy. piv@unife.it
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Piva
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Lambertini
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Penolazzi
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Nastruzzi
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics*; D002470:Cell Survival; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005229:Fatty Acids, Monounsaturated; D005260:Female; D005456:Fluorescent Dyes; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D008081:Liposomes; D010713:Phosphatidylcholines; D011401:Promoter Regions, Genetic; D000644:Quaternary Ammonium Compounds; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
D005229:Fatty Acids, Monounsaturated; D005456:Fluorescent Dyes; D008081:Liposomes; D010713:Phosphatidylcholines; D000644:Quaternary Ammonium Compounds; D011960:Receptors, Estrogen; D004247:DNA; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane