Tamoxifen inhibits transforming growth factor-alpha gene expression in human breast carcinoma samples treated with

S J Conde1, R A M Luvizotto, M T Síbio

  • 1Division of Endocrinology and Metabolism, Department of Medical Clinic, UNESP, Botucatu, Brazil.

Abstract

Insights

Triiodothyronine (T3) significantly increased transforming growth factor-alpha (TGF-alpha) mRNA in breast cancer cells. Tamoxifen (TAM) mitigated T3

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Estrogen receptor (ER) and thyroid hormone receptor expression are common in breast cancer.
  • Transforming growth factor-alpha (TGF-alpha) is a mitogenic protein implicated in cancer progression.

Purpose of the Study:

  • To investigate the effects of triiodothyronine (T3), 17beta-estradiol (E2), and tamoxifen (TAM) on TGF-alpha gene expression in primary breast cancer.
  • To explore the interactions between these treatments on TGF-alpha expression.

Main Methods:

  • Primary human breast carcinoma tissues were cultured.
  • Tissues were treated with T3, E2, TAM, or combinations thereof.
  • TGF-alpha mRNA levels were quantified via quantitative real-time PCR.

Main Results:

  • T3 treatment significantly upregulated TGF-alpha mRNA (15-fold increase).
  • Concomitant TAM treatment reduced T3-induced TGF-alpha expression (3.4-fold increase).
  • Tamoxifen alone increased TGF-alpha mRNA expression (5.3-fold increase).

Conclusions:

  • T3 is a more potent inducer of TGF-alpha mRNA than E2 in breast cancer primary cultures.
  • TAM exhibits a mitigating effect on T3-induced TGF-alpha upregulation.
  • TAM alone can induce TGF-alpha, suggesting a potential mitogenic role independent of E2, possibly influenced by ER subtypes.

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