Tamoxifen inhibits transforming growth factor-alpha gene expression in human breast carcinoma samples treated with triiodothyronine.
J Endocrinol Invest
; 31(12): 1047-51, 2008 Dec.
Article
em En
| MEDLINE
| ID: mdl-19246968
ABSTRACT
OBJECTIVES:
To examine the effects of triiodothyronine (T3), 17beta-estradiol (E2), and tamoxifen (TAM) on transforming growth factor (TGF)-alpha gene expression in primary breast cancer cell cultures and interactions between the different treatments. METHODS ANDRESULTS:
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-alpha 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-alpha 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-alpha mRNA expression increased 5.3-fold, significantly higher than with all other treatment modalities.CONCLUSION:
We demonstrate that TGF-alpha 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-alpha upregulation. Our findings show some similarities between primary culture and breast cancer cell lines, but also some important differences a) induction of TGF-alpha, a mitogenic protein, by TAM; b) a differential effect of TAM that may depend on relative expression of ER alpha and beta; and c) supraphysiological doses of T3 may induce mitogenic signals in breast cancer tissue under conditions of low circulating E2.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tamoxifeno
/
Tri-Iodotironina
/
Neoplasias da Mama
/
Carcinoma
/
Fator de Crescimento Transformador alfa
Limite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
J Endocrinol Invest
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Brasil