15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Differential effects of aromatase inhibitors and antiestrogens on estrogen receptor expression in breast cancer cells.

      Anticancer research
      Aromatase Inhibitors, therapeutic use, Blotting, Western, Breast Neoplasms, drug therapy, metabolism, Estradiol, analogs & derivatives, Estrogen Antagonists, Estrogen Receptor alpha, antagonists & inhibitors, genetics, Estrogen Receptor beta, Female, Humans, Neoplasm Staging, Neoplasms, Hormone-Dependent, Nitriles, Prognosis, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Tamoxifen, Triazoles, Tumor Cells, Cultured

      Read this article at

      ScienceOpenPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Estrogen receptors (ER) alpha and beta play an important role in breast cancer. Recently, systemic adjuvant endocrine therapy with selective estrogen receptor modulator (SERM) tamoxifen has been challenged by aromatase inhibitors. Compared to antiestrogens, third-generation aromatase inhibitors (anastrozole and letrozole) exhibit an improved efficacy and tolerability. Using real-time PCR analysis, 21 breast cancer tissue samples were analysed for a change of the ERalpha/ERbeta ratio during malignant progression. In stimulation experiments, differential effects of SERMs, ER antagonists and aromatase inhibitors have been investigated. Transition from normal breast to grade 1 tumors was characterized by down-regulation of ERbeta (relative quantification [RQ]=0.83, p=0.019), while transition from grade 1 to grade 3 tumors was associated with the decrease of ERalpha expression (RQ=1.14 vs. RQ=0.65, p<0.001). In stimulation assays, tamoxifen and fulvestrant increased ERalpha expression to RQ=1.51 (p=0.01) and RQ=1.42 (p<0.001), respectively, and left ERbeta unchanged. In contrast, aromatase inhibitors up-regulated ERbeta to RQ=1.23 (anastrozole, p=0.029) and RQ=1.38 (letrozole, p=0.048). Taken together, data indicate that SERMs/antiestrogens and aromatase inhibitors exhibit opposed effects on the ER expression of breast cancer cells: tamoxifen and fulvestrant up-regulate ERalpha expression, while aromatase inhibitors increase ERbeta expression, which may contribute to the aromatase inhibitors' therapeutic superiority over antiestrogens.

          Related collections

          Author and article information

          Comments

          Comment on this article