Phospholipase A and breast cancer

Abstract

Dysregulated eicosanoid signalling is emerging as a crucial factor in diverse disease processes that include oncogenesis. Breast carcinoma progression is the result of the subversion of multiple intracellular signalling pathways found in normal mammary tissue that impact upon the differentiation, proliferation and survival of tumour cells, as well as the stimulation of angiogenesis. Phospholipase A (PLA), as the enzyme initiating arachidonic acid release from membrane phospholipids, is located at a critical junction between hormone- and growth factor-regulated signalling cascades. PLA itself or the other enzymes that catalyse downstream eicosanoid metabolism may provide novel therapeutic targets for the treatment of breast carcinoma. This review describes the contribution of PLA and its products to the progression of breast carcinoma and the interaction of eicosanoid signalling with other cascades modulated by oestrogen, epidermal growth factor, signal transducers and activators of transcription, mammalian target of rapamycin and also cell metabolism in tumour cells.