Effects of tamoxifen on transcriptional level of transforming growth factor beta (TGF-beta) isoforms 1 and 2 in tumor tissue during primary treatment of patients with breast cancer.

摘要

Tamoxifen action in breast cancer is believed to be mediated in part by regulation of transforming growth factor beta (TGF-beta) isoforms in tumor tissue. However, the pattern of this regulation and its relation ship to clinical data are not yet clearly understood. Tumor tissue was derived from 10 patients with breast cancer before and following primary treatment with tamoxifen over a period of 1-12 days, preceding tumor ectomy. Each tissue sample was processed for semiquantitative assessment of the mRNA expression levels of the TGF-beta isoforms 1 and 2 using competitive RT-PCR. The results of mRNA quantification were then related to the estrogen receptor-alpha (ER-alpha) and progesterone receptor (PR) status of the tumors as well as to the clinical course during the first 5-6 postoperative years in patients who additionally received adjuvant tamoxifen therapy. TGF-beta 1 mRNA and TGF-beta 2 mRNA expression was detectable in all examined samples. During treatment with tamoxifen, the TGF-beta 2 mRNA level changed in 8 cases, increasing seven times and decreasing once, whereas the TGF-beta 1 mRNA level changed in only two cases, increasing once and decreasing once. Our data do not provide evidence of a strong correlation between the occurrence of tamoxifen-related induction of TGF-beta 2 mRNA expression and the ER-alpha or PR status. The prediction sensitivity of the response to adjuvant therapy, to which relapse-free survival during post-operative follow-up over 5-6 years was attributed, increased when the tamoxifen-related up-regulation of the TGF-beta 2 mRNA level was considered to predict response, in addition to the ER-alpha- and/or PR-rich receptor status. We conclude that tamoxifen predominantly induces an up-regulation of TFG-beta 2 expression on the transcriptional level in breast cancer, which may predict clinical response independently of the ER-alpha/PR status in some cases.