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Published online 4 June 2004

Nucleic Acids Research, 2004, Vol. 32, No. 10 3065-3069
© 2004 Oxford University Press

Inhibition of human breast carcinoma proliferation, migration, chemoinvasion and solid tumour growth by DNAzymes targeting the zinc finger transcription factor EGR-1

Ainslie Mitchell, Crispin R. Dass1, Lun-Quan Sun1 and Levon M. Khachigian*

Department of Haematology, Centre for Vascular Research, The University of New South Wales, Sydney NSW 2052, Australia and 1 Johnson and Johnson Research Pty Limited, Sydney, Australia

*To whom correspondence should be addressed. Tel: +61 2 9385 2537; Fax: +61 2 9385 1389; Email: L.Khachigian{at}unsw.edu.au

Received April 22, 2004; Revised and Accepted May 10, 2004

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.


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