Akademik Veri Yönetim Sistemi
MEDICAL HYPOTHESES, cilt.63, sa.4, ss.684-687, 2004 (SCI-Expanded)
Estrogen is the main stimulant in the development and growth of breast cancer. The estrogen receptor antagonist tamoxifen has been mainstay of hormonal therapy. Although tamoxifen has been an effective adjuvant therapy, approximately 30% of patients treated with this agent still die within 10 years of follow-up treatment, and relapses can occur for greater than or equal to 20 years following therapy. However, the underlying cause of treatment failure in many breast cancer patients receiving tamoxifen is resistance to tamoxifen. ERbeta may influence estrogen action through the ERalpha pathway and the hormone refractoriness of breast cancer. ERbetacx, the carboxy terminal splicing variant of ERbeta, has been considered a dominant repressor of ERalpha function, because ERbetacx inhibits transcriptional activity of ERalpha rather than ERbeta wild type (wt). Tamoxifen responders tended to exhibit a tower ratio of ERbetacx to ERbetawt than non-responders. Induction of ERbeta reduces growth of exponentially proliferating cells. Since the promoter region of ERbeta is rich in CpG dinucleotides, loss of expression of ERbeta observed in some tumours could be due to aberrant methylation of CpG islands. Treatment of ERbeta-negative cell lines with DNA methyl transferase inhibitors restored ERbeta expression, providing experimental evidence that silencing of ERbeta in breast carcinomas could be due to promoter hypermethylation. Procainamide, used for cardiac arrhythmias, has been proposed as being a non-nucleoside inhibitor of DNA methylation and also demthylates and reactivate tumor suppressor genes in breast cancer cell tines. Therefore, concomitant use of procainamide with tamoxifen in ERalpha-positive and ERbeta-negative breast cancers may increase the tamoxifen response. Procainamide, given orally may also be used in breast cancer patients who developed resistance during the tamoxifen treatment. In vivo and in vitro studies evaluating effectiveness of concomitant use of procainamide and tamoxifen in tamoxifen resistant and ERbeta-negative breast cancer may further support our hypothesis. (C) 2004 Elsevier Ltd. All rights reserved.