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Int J Oncol. 2002 Jul;21(1):153-7.

Beta-adrenergic and arachidonic acid-mediated growth regulation of human breast cancer cell lines.

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Experimental Oncology Laboratory, Carcinogenesis and Developmental Therapeutics Program, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.


Adenocarcinoma of the mammary gland is the leading type of cancer in women. Among these breast cancers those that are estrogen-responsive respond well to existing therapeutic regimens while estrogen non-responsive cancers metastasize widely, demonstrate a high relapse rate, and respond poorly to therapy. Over-expression of the arachidonic acid-metabolizing enzymes cyclooxygenase-2 and lypoxygenases is frequently observed in breast cancer, particularly the non-estrogen-responsive type, suggesting a role of the arachidonic acid (AA) cascade in the growth regulation of these malignancies. Adenocarcinomas of the lungs, pancreas and colon also frequently over-express AA-metabolizing enzymes, and recent evidence suggests that the growth-regulating AA-cascade in these malignancies is under beta-adrenergic control. Our current experiments have therefore tested the hypothesis that in analogy to these findings adenocarcinomas of the breast are also regulated by beta-adrenergic receptors via stimulation of the AA-cascade. Analysis of DNA synthesis by [3H]-thymidine incorporation assays in three estrogen-responsive and three estrogen non-responsive cell lines derived from human breast cancers demonstrated a significant reduction in DNA synthesis by beta-blockers and inhibitors of cyclooxygenase or lipoxygenases in all cell lines. Analysis of AA-release in one of the most responsive cell lines demonstrated a time-dependent increase in AA-release in response to the beta-adrenergic agonist isoproterenol. Analysis by RT-PCR revealed expression of beta2-adrenergic receptors in all cell lines whereas beta1-adrenergic receptors were not found in two of the estrogen non-responsive cell lines. Our data suggest that a significant subset of human breast cancers is under control of beta-adrenergic receptors via stimulation of the AA-cascade. These findings open up novel avenues for the prevention and clinical management of breast cancer, particularly the non-estrogen-responsive types. Moreover, our findings suggest that cardiovascular disease and adenocarcinomas in a variety of organ systems, including the breast may share common risk factors and benefit from similar preventive and treatment strategies.

[Indexed for MEDLINE]

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