Inhibition of human breast carcinoma proliferation, migration, chemoinvasion and solid tumour growth by DNAzymes targeting the zinc finger transcription factor EGR-1.
DNAzymes (synthetic catalytic DNA) have emerged as a new class of nucleic acid-based gene silencing agent. Using DNAzymes targeting the human mRNA of the immediate-early gene and C2H2-class zinc finger transcription factor early growth response-1 (EGR-1), we demonstrate here that EGR-1 plays an indispensable role in breast cancer proliferation, migration, chemoinvasion and xenograft growth in nude mice. DNAzyme inhibition of these tumorigenic processes and EGR-1 protein expression in breast carcinoma cells is sequence-specific and EGR-1 transcription-independent. These agents inhibit breast carcinoma cell migration and chemoinvasion in microchemotaxis chambers and solid tumour growth in athymic nude mice. Thus, DNAzymes targeting specific genes can inhibit multiple key tumorigenic processes in vitro and in vivo and may serve as useful anti-cancer agents.
Mitchell
Ainslie
A
Department of Haematology, Centre for Vascular Research, The University of New South Wales, Sydney, NSW 2052, Australia.
Dass
Crispin R
CR
Sun
Lun-Quan
LQ
Khachigian
Levon M
LM
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D021881:DNA, Catalytic / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D051766:Early Growth Response Protein 1; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*
D000970:Antineoplastic Agents; D021881:DNA, Catalytic; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D014157:Transcription Factors