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

4. REGULATION OF LIPOXYGENASE BY GROWTH FACTORS AND CYTOKINES

Evidence suggests that tumor cells as well as several normal cells have LO activity (18) and both arachidonic acid as well as linoleic acids are converted to LO products such as HETEs and hydroxyoctadecadienoic acids (HODEs). The 12-LO and 15-LO pathways can be activated by growth factors and cytokines. In A431 epidermoid carcinoma cells, epidermal growth factor (EGF) could induce platelet 12-LO mRNA expression (19,20). Recent studies have indicated that EGF can stimulate 13-HODE formation in BT-20 breast cancer cells by a 15-LO-dependent mechanism (21). Human vascular smooth muscle cell 12-LO expression was increased by treatment with angiotensin II (12,14), while human monocyte 15-LO was induced by interleukin-4 and interleukin-13 (22,23). Porcine 12-LO in vascular smooth muscle cells was also markedly upregulated by platelet-derived growth factor (24) and by cytokines such as interleukins-1, -4 and -8 (25). Thus, increased leukocyte-type 12-LO activity and expression may play a role in the growth-promoting effects of these factors.