ROLE OF LIPOXYGENASES IN BREAST CANCER

Rama Natarajan and Jerry Nadler

Department of Diabetes, Endocrinology and Metabolism¹, City of Hope National Medical Center, 1500, E. Duarte Road, Duarte, California 91010, USA.

Received 5/15/98 Accepted 5/29/98

8. PERSPECTIVE

Increased activity and expression of LO enzymes in tumor cells can lead to excess accummulation of products with potent growth promoting, chemotactic, inflammatory and angiogenic effects, which therefore implicate them in the pathogenesis of breast cancer. There are currently no clinically available safe and selective inhibitors of 12-LO enzymes. One approach could be to use gene therapy to block these enzymes. We have developed a novel ribozyme or catalytic RNA directed against the porcine leukocyte 12-LO (63). We showed that this ribozyme can efficiently cleave 12-LO mRNA in vitro and can also dose-dependently decrease 12-lipoxygenase mRNA and protein expression when transfected into porcine vascular smooth muscle cells (63,64). Hence, therapeutic modalities and novel ribozyme technology approaches to effectively block these pathways may provide new anti cancer therapies.