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

Autor(es)

Conde, S. J. ; Luvizotto, R. A. M. ; Sibio, M. T. ; Katayama, M. L. H. ^[1] ; Brentani, M. M. ^[1] ; Nogueira, C. R. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Radiol, Div Oncol, BR-09500900 Sao Paulo - Brazil

^[2] UNESP, Fac Med, Dept Clin Med, Div Endocrinol & Metab, BR-18618970 Botucatu, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Endocrinological Investigation; v. 31, n. 12, p. 1047-1051, DEC 2008.
• Citações Web of Science: 13

Resumo

Objectives: To examine the effects of triiodothyronine (T(3)), 17 beta-estradiol (E(2)), and tamoxifen (TAM) on transforming growth factor (TGF)-alpha 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: T(3); dish 3: T(3)+TAM; dish 4: TAM; dish 5: E(2); dish 6: E(2)+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 T(3) 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 T(3) than E(2). Concomitant treatment with TAM had a mitigating effect on the T(3) effect, while E(2) 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 E(2).. Endocrinol. Invest. 31: 1047-1051, 2008) (c) 2008, Editrice Kurtis (AU)

• Processo FAPESP: 04/12338-7 - Interrelacao da modulacao genica por estrogeno (e2) e triodotironina (t3) em cultura primaria de adenocarcinoma de mama.
• Beneficiário: Celia Regina Nogueira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 05/55459-1 - Interrelação da modulação gênica por estrógeno (E2) e triiodotironina (T3) em cultura primária de adenocarcinoma de mama
• Beneficiário: Sandro José Conde
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto