Triiodothyronine (T3) induces HIF1A and TGFA expression in MCF7 cells by activating PI3K.
High expression levels of hypoxia inducing factor 1 alpha are related to mammary carcinogenesis. In previous studies, we demonstrated that expression of transforming growth factor alpha increases upon treatment with triiodothyronine, but this expression does not occur in cellular models that do not express the estrogen receptor, or when cells are co-treated with the anti-estrogen, tamoxifen. The aim of this study was to determine the effect of the hormone triiodothyronine on the expression of the genes HIF1A and TGFA in the breast cancer cell line MCF7. The cell line was subjected to treatment with triiodothyronine at the supraphysiological dose of 10(-8)M for 10min, 30min, 1h, and 4h in the presence or absence of actinomycin D, the gene expression inhibitor, cycloheximide, the protein synthesis inhibitor, and LY294002, the phosphoinositide 3 kinase inhibitor. HIF1A and TGFA mRNA expression was analyzed by reverse transcription polymerase chain reaction. For data analysis, we used analysis of variance complemented by Tukey test and an adopted minimum of 5% significance. We found that HIF1A and TGFA expression increased in the presence of triiodothyronine at all times studied. HIF1A expression decreased in triiodothyronine-treated cells when gene transcription was also inhibited; however, TGFA expression decreased after 10 and 30min of treatment even when transcription was not inhibited. We found that activation of PI3K was necessary for triiodothyronine to modulate HIF1A and TGFA expression.
Department of Internal Medicine, Botucatu Medical School, Univ Estadual Paulista - UNESP, Botucatu, SP 18618-970, Brazil. Electronic address: fer_fontesbtu@hotmail.com.
Fernanda Cristina Fontes
FC
Moretto
Department of Internal Medicine, Botucatu Medical School, Univ Estadual Paulista - UNESP, Botucatu, SP 18618-970, Brazil.
Maria Teresa
MT
De Sibio
Department of Pathology, Botucatu Medical School, Univ Estadual Paulista - UNESP, Botucatu, SP 18618-970, Brazil.
Aline Carbonera
AC
Luvizon
Department of Internal Medicine, Botucatu Medical School, Univ Estadual Paulista - UNESP, Botucatu, SP 18618-970, Brazil.
Regiane Marques Castro
RM
Olimpio
Department of Internal Medicine, Botucatu Medical School, Univ Estadual Paulista - UNESP, Botucatu, SP 18618-970, Brazil.
Miriane
M
de Oliveira
Department of Morphology, Bioscience Institute, Univ Estadual Paulista - UNESP, Botucatu, SP 18618-970, Brazil.
Carlos Augusto Barnabe
CA
Alves
Department of Internal Medicine, Botucatu Medical School, Univ Estadual Paulista - UNESP, Botucatu, SP 18618-970, Brazil.
Sandro José
SJ
Conde
Department of Internal Medicine, Botucatu Medical School, Univ Estadual Paulista - UNESP, Botucatu, SP 18618-970, Brazil.
Célia Regina
CR
Nogueira
D004789:Enzyme Activation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D061986:MCF-7 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000235:genetics*; D014284:Triiodothyronine / Q000502:physiology*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016211:Transforming Growth Factor alpha; D014284:Triiodothyronine; D019869:Phosphatidylinositol 3-Kinases
Breast cancer; Extra-nuclear pathway; Gene expression; Thyroid hormone