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

  • Authors:
    • Y. Cakir
    • H. K. Plummer
    • P. K. Tithof
    • H. M. Schuller
  • View Affiliations

  • Published online on: July 1, 2002     https://doi.org/10.3892/ijo.21.1.153
  • Pages: 153-157
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Abstract

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 β-adrenergic control. Our current experiments have therefore tested the hypothesis that in analogy to these findings adenocarcinomas of the breast are also regulated by β-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 β-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 β-adrenergic agonist isoproterenol. Analysis by RT-PCR revealed expression of β2-adrenergic receptors in all cell lines whereas β1-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 β-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.

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July 2002
Volume 21 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Cakir Y, Plummer HK, Tithof PK and Schuller HM: Beta-adrenergic and arachidonic acid-mediated growth regulation of human breast cancer cell lines. Int J Oncol 21: 153-157, 2002
APA
Cakir, Y., Plummer, H.K., Tithof, P.K., & Schuller, H.M. (2002). Beta-adrenergic and arachidonic acid-mediated growth regulation of human breast cancer cell lines. International Journal of Oncology, 21, 153-157. https://doi.org/10.3892/ijo.21.1.153
MLA
Cakir, Y., Plummer, H. K., Tithof, P. K., Schuller, H. M."Beta-adrenergic and arachidonic acid-mediated growth regulation of human breast cancer cell lines". International Journal of Oncology 21.1 (2002): 153-157.
Chicago
Cakir, Y., Plummer, H. K., Tithof, P. K., Schuller, H. M."Beta-adrenergic and arachidonic acid-mediated growth regulation of human breast cancer cell lines". International Journal of Oncology 21, no. 1 (2002): 153-157. https://doi.org/10.3892/ijo.21.1.153