Beta-adrenergic and arachidonic acid-mediated growth regulation of human breast cancer cell lines
| Autor: | Y, Cakir, H K, Plummer, P K, Tithof, H M, Schuller |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
DNA Replication
Arachidonate 5-Lipoxygenase Arachidonic Acid Neoplasms Hormone-Dependent Aspirin Cyclooxygenase 2 Inhibitors Reverse Transcriptase Polymerase Chain Reaction Adrenergic beta-Antagonists Isoproterenol Membrane Proteins Breast Neoplasms Estrogens DNA Adrenergic beta-Agonists Isoenzymes Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Tumor Cells Cultured Humans Cyclooxygenase Inhibitors Female Lipoxygenase Inhibitors RNA Messenger Receptors Adrenergic beta-2 Enzyme Inhibitors |
| Zdroj: | International journal of oncology. 21(1) |
| ISSN: | 1019-6439 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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