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

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Abstract

Objectives: To examine the effects of triiodothyronine (T3), 17β-estradiol (E2), and tamoxifen (TAM) on transforming growth factor (TGF)-α gene expression in primary breast cancer cell cultures and interactions between the different treatments. Methods and results: Patients included in the study (no.=12) had been newly diagnosed with breast cancer. Fresh human breast carcinoma tissue was cut into 0.3-mm slices. These slices were placed in six 35-mm dishes on 2-ml organ culture medium. Dishes received the following treatments: dish 1: ethanol; dish 2: T3; dish 3: T3+TAM; dish 4: TAM; dish 5: E2; dish 6: E2+TAM. TGF-α mRNA content was normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA levels. All tissues included in this study were positive for estrogen receptor (ER) and thyroid hormone receptor expression. Treatment with T3 for 48 h significantly increased TGF-α mRNA levels compared to controls (15-fold), and concomitant treatment with TAM reduced expression to 3.4-fold compared to controls. When only TAM was added to the culture medium, TGF-α mRNA expression increased 5.3-fold, significantly higher than with all other treatment modalities. Conclusion: We demonstrate that TGF-α mRNA expression is more efficiently upregulated by T3 than E2. Concomitant treatment with TAM had a mitigating effect on the T3 effect, while E2 induced TGF-α upregulation. Our findings show some similarities between primary culture and breast cancer cell lines, but also some important differences: a) induction of TGF-α, a mitogenic protein, by TAM; b) a differential effect of TAM that may depend on relative expression of ER α and β; and c) supraphysiological doses of T3 may induce mitogenic signals in breast cancer tissue under conditions of low circulating E2.

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Authors and Affiliations

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

    S. J. Conde, R. A. M. Luvizotto, M. T. Síbio & C. R. Nogueira MD, PhD

  2. Division of Oncology, Department of Radiology, USP, São Paulo, Brazil

    M. L. H. Katayama & M. M. Brentani

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  1. S. J. Conde
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  2. R. A. M. Luvizotto
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  3. M. T. Síbio
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  4. M. L. H. Katayama
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  5. M. M. Brentani
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  6. C. R. Nogueira MD, PhD
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Correspondence to C. R. Nogueira MD, PhD.

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Conde, S.J., Luvizotto, R.A.M., Síbio, M.T. et al. Tamoxifen inhibits transforming growth factor-α gene expression in human breast carcinoma samples treated with triiodothyronine. J Endocrinol Invest 31, 1047–1051 (2008). https://doi.org/10.1007/BF03345650

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