Genetic induction and upregulation of cyclooxygenase (COX) and aromatase (CYP19): an extension of the dietary fat hypothesis of breast cancer

A novel model of mammary carcinogenesis is proposed involving sequential in duction and upregulation of cyclooxygenase and aromatase genes by essential fatty acids prominent in the US diet. The basic carcinogenic processes are : (1) constitutive prostaglandin biosynthesis and formation of mutagenic ox ygen and nitrogen free radicals responsible for tumor initiation; (2) PGE-2 -induced expression of aromatase and constitutive estrogen biosynthesis whi ch sustains mitogenesis and tumor promotion; and (3) PGE-2-induced expressi on of vascular endothelial growth factor which stimulates angiogenesis and tumor metastasis.