Changes in expression of transforming growth factor beta mRNA isoforms in patients undergoing tamoxifen therapy

Abstract

Tumour was obtained from 37 patients with oestrogen receptor-positive breast cancer, before and during treatment with tamoxifen, and examined qualitatively and semi-qualitatively for mRNA of the three mammalian TGF-beta isoforms. Levels of TGF-beta isoforms were then correlated with tumour response to tamoxifen, as assessed by monthly ultrasound. A high incidence of expression by each isoform was found in tumour material taken both before and during treatment. Semiquantitative assessment of mRNA showed that in the majority of tumours, expression of TGF-beta s did not change markedly with treatment, i.e. beyond that which might have been caused by method reproducibility and tumour heterogeneity (variations of < 100% between pre- and post-treatment samples). In those displaying significant variation with treatment, expression of TGF-beta 1 and -beta 3 increased or decreased in equal numbers, whereas TGF-beta 2 expression tended to increase with treatment. Subdividing tumours by clinical response revealed no significant association between changes in expression of TGF-beta 1 and TGF-beta 3. There was, however, a significant correlation between changes in expression of TGF-beta 2 and response (P = 0.018). Thus, of 15 responding tumours displaying substantial changes, 11 showed an increase in TGF-beta 2 expression with treatment, whereas none of the non-responding tumours were associated with increased expression. While not providing evidence for a generalised increase in TGF-beta expression with tamoxifen treatment, the present study suggests that response to tamoxifen therapy may be associated with an increase in expression of specific TGF-beta isoforms in some, but not all, tumours.