COX2 and BC a cumulative knowledge thread

[R.B.]

Two mechanisms are recognised here - gene expression and enzyme activity.

RB

Cyclooxygenase-2 directly regulates gene expression of P450 Cyp19 aromatase promoter regions pII, pI.3 and pI.7 and estradiol production in human breast tumor cells.
Prosperi JR, Robertson FM.

Department of Molecular Virology, Immunology, and Medical Genetics, The Integrated Biomedical Science Graduate Program, The Ohio State University College of Medicine, 2184 Graves Hall, 333 West 10th Avenue, Columbus, OH 43210, USA.

"These studies demonstrate that Cox-2 directly regulates gene expression of specific aromatase promoter regions and regulates aromatase enzyme activity. Agents that inhibit Cox-2 or block the biological effects of PGE2 may be useful in significantly limiting aromatase activity and proliferation of human breast tumor cells regardless of the presence of Cox-2."

[R.B.]

Reduced BRAC1 increases aromatase products.

It looks as if BRAC 1 may act as an aromatase inhibitor (and when BRAC1 mutates does it stop doing that ? - this seems to be the question being asked between the lines)

BRCA1 negatively regulates the cancer-associated aromatase promoters I.3 and II in breast adipose fibroblasts and malignant epithelial cells.
Lu M, Chen D, Lin Z, Reierstad S, Trauernicht AM, Boyer TG, Bulun SE.

http://www.ncbi.nlm.nih.gov/sites/en...ubmed_RVDocSum

Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.

"CONCLUSIONS: Selective inhibition of aromatase expression by BRCA1 binding to the I.3/II tumorigenic promoter region may be an important protective mechanism against breast cancer development."

[R.B.]

Thought provoking indeed.

RB



HER-2/neu status is a determinant of mammary aromatase activity in vivo: evidence for a cyclooxygenase-2-dependent mechanism.
Subbaramaiah K, Howe LR, Port ER, Brogi E, Fishman J, Liu CH, Hla T, Hudis C, Dannenberg AJ.

Department of Medicine, Weill Medical College of Cornell University, New York, NY, USA.

http://www.ncbi.nlm.nih.gov/sites/en...ubmed_RVDocSum

"Previously, we found that overexpression of HER-2/neu was associated with increased levels of COX-2 in human breast cancers. Here, we show that overexpression of HER-2/neu is also associated with increased aromatase activity. These results suggested the possibility that COX-2 was the functional intermediate linking HER-2/neu and aromatase......Collectively, our data indicate that COX-2 is the functional intermediate linking HER-2/neu and aromatase and suggest that inhibitors of PGE(2) synthesis will suppress estrogen biosynthesis in breast tissue."