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 induction 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 oxygen and nitrogen free radicals responsible for tumor initiation; (2) PGE-2-induced expression of aromatase and constitutive estrogen biosynthesis which sustains mitogenesis and tumor promotion; and (3) PGE-2-induced expression of vascular endothelial growth factor which stimulates angiogenesis and tumor metastasis.
Harris
R E
RE
The Ohio State University Comprehensive Cancer Center, Columbus 43210-1240, USA.
Robertson
F M
FM
Abou-Issa
H M
HM
Farrar
W B
WB
Brueggemeier
R
R
D001141:Aromatase / Q000096:biosynthesis / Q000235:genetics*; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004041:Dietary Fats; D004790:Enzyme Induction; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D008565:Membrane Proteins; D008957:Models, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics*
D004041:Dietary Fats; D007527:Isoenzymes; D008565:Membrane Proteins; D001141:Aromatase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases