Role of lipoxygenases in breast cancer.
The interaction of growth factors such as epidermal growth factor (EGF) with their receptors on breast cancer cells can lead to the hydrolysis of phospholipids and release of fatty acids such as arachidonic acid which can be further metabolized by the lipoxygenase (LO) pathway. Several LO products have been shown to stimulate oncogenes and have mitogenic and chemotactic effects. The 12-LO product, 12-hydroxyeicosatetraenoic acid (12(S)HETE), has been shown to play a key role in mediating several steps of the process of hematogenous metastasis and tumor cell adhesion. 12-LO can also be activated by several growth factors and inflammatory cytokines. A growing body of evidence suggests that specific metabolites of arachidonic and/or linoleic acid serve as central elements in signal pathways necessary for cell mitogenesis as induced by growth factors or oncogenic transformation. This review examines the role of LOs in breast cancer. The growth of breast cancer cells has been shown to increased by certain LO products and, LO pathway inhibitors could block the growth of some breast cancer cells. 12-LO activity and expression was increased in breast cancer tissues relative to the uninvolved normal tissue, and also in cultured breast cancer cells relative to normal breast cells. Treatment of the breast cancer cell line, MCF-7 cells, with epidermal growth factor (EGF), led to significant increases in 12-LO activity and expression. Thus, activation of the 12-LO pathway may play a key role in basal and EGF-induced breast cancer cell growth.
Natarajan
R
R
Department of Diabetes, Endocrinology and Metabolism, City of Hope National Medical Center, 1500, E. Duarte Road, Duarte, California 91010, USA.
Nadler
J
J
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D001092:Arachidonate 12-Lipoxygenase / Q000096:biosynthesis; D001093:Arachidonate 15-Lipoxygenase / Q000096:biosynthesis; D001095:Arachidonic Acids / Q000378:metabolism; D001940:Breast / Q000201:enzymology / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D008084:Lipoxygenase / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D006133:Growth Substances; D012333:RNA, Messenger; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D004815:Epidermal Growth Factor; D008084:Lipoxygenase; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase