Involvement of Triiodothyronine (T3) on Tgfa expression in a Breast Adenocarcinoma Cell Line
Presentation Number: SUN 266
Date of Presentation: April 2nd, 2017
Fernanda Cristina Fontes Moretto*1, Maria Teresa De Sibio2, Regiane Marques Castro Olimpio3, Miriane de Oliveira1, Bianca Mariani Gonçalves3, Lucas Solla Mathias3, Igor de Carvalho Depra4, Gilberto J. Paz-Filho5 and Celia R Nogueira6
1Botucatu School of Medicine, University of São Paulo State, Brazil, Botucatu, BRAZIL, 2Botucatu School of Medicine, University of São Paulo State, Brazil, Botucatu, Brazil, 3Botucatu School of Medicine, University of São Paulo State, Brazil, Botucatu, 4Botucatu School of Medicine, University of São Paulo State, Brazil., Dept .of Medicina, 5Australian National University, Acton, Australia, 6Botucatu School of Medicine, University of São Paulo State, Brazil., Botucatu
Title: INVOLVEMENT OF TRIIODOTHYRONINE (T3) ON TGFA EXPRESSION IN A BREAST ADENOCARCINOMA CELL LINE.
Introduction: a myriad of environmental risk factors, pathological conditions and physiological agents, such as thyroid hormones (TH), have been proposed to influence the development of breast cancer (BC). Triiodothyronine (T3) has been shown to increase adenocarcinoma cancer cell proliferation in vitro. Many tumors induce the transcription of a number of genes related to angiogenesis, exhibiting the superexpression of transforming growth factor, alpha subunit (TGFA), which is positively correlated with tumor aggressiveness and malignant progression. However, it is largely unknown whether T3 affects TGFA expression.
Objective: To elucidate the modes of action of T3, aiming at verifying TGFA mRNA expression in the breast adenocarcinoma cell line MCF-7, using specific drugs to block intracellular signaling pathways.
Methods: MCF-7 breast adenocarcinoma cells were subjected to treatment with 10-8M T3 for 1h, alone or combined with the ERK/MAPK inhibitors PD98059 (PD),the integrin αvβ3inhibitor RGD peptide (RGD), or α-amanitin (AM), a specific inhibitor of RNA polymerase II. Appropriate control groups were employed. TGFA mRNA was assayed by RT-PCR. Statistical analysis was performed by ANOVA for completely random model, complemented with Tukey test for multiple comparisons, regarding a 5% significance level.
Results: TGFA gene expression was increased in the presence of T3 (1±0,03) when compared to the control group (4,9±0,46), in contrast to the groups treated only with the inhibitors (PD, RGD, or AM), in which no significant difference was present. We observed that the expression of TGFA were increased in the T3 group associated with AM (4,6±0,04), compared to AM only (1,05±0,05). Nonetheless, the associated treatments all (T3+PD 2,63±0,18; T3+RGD 2,22±0,21 and T3+AM 4,60±0,04) had significantly lower TGFA gene expression compared to T3 alone.
Conclusion: Our study showed that T3 increases TGFA expression, even with transcription inhibition, and acts through extranuclear pathways in MCF-7 cells. The data obtained present a great potential for application, since the identification of new signaling pathways and other mecanisms by which thyroid hormones act can lead to the development of specific drugs, to activate or block such pathways, promoting desirable effects and blocking undesirable ones.
Nothing to Disclose: FCFM, MTD, RMCO, MDO, BMG, LSM, IDCD, GJP, CRN