Correlation of aromatase and cyclooxygenase gene expression in human breast cancer specimens.
Aromatase, the enzyme system catalyzing estrogen biosynthesis, is found in stromal tissue in the breast. The increased expression of the aromatase CYP19 gene in breast cancer tissues was recently associated with a promoter region regulated through cAMP-mediated pathways. PGE2, derived from cyclooxygenase, increases intracellular cAMP levels and stimulates estrogen biosynthesis. This association suggest that local production of PGE2 via cyclooxgenase isozymes may influence estrogen biosynthesis. The present study represents the first to examine the levels of mRNA expression of CYP19, COX-1, and COX-2 genes in human breast cancer specimens and normal breast tissue samples using semi-quantitative RT-PCR methods. Positive correlations were observed between CYP19 and COX-2 and the greater extent of breast cancer cellularity. Linear regression analysis using a bivariate model shows a strong linear association between CYP19 expression and the sum of COX-1 and COX-2 expression. This significant relationship between the aromatase and cyclooxygenase enzyme systems suggests that autocrine and paracrine mechanisms may be involved in hormone-dependent breast cancer development via growth stimulation from local estrogen biosynthesis.
Brueggemeier
R W
RW
College of Pharmacy, The Ohio State University, Columbus 43210-1291, USA. brueggemeier.1@osu.edu
Quinn
A L
AL
Parrett
M L
ML
Joarder
F S
FS
Harris
R E
RE
Robertson
F M
FM
D001141:Aromatase / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007527:Isoenzymes / Q000096:biosynthesis; D016014:Linear Models; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
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