Angiotensin-(1 - 7) and Human Chorionic Gonadotropin (hCG) Modulate the Nuclear Transcription Factors or Nuclear Receptors Genes in the Tumorigenic Undifferentiated Breast Cancer Cell Line SKBR3

Isidoro Binda Neto, Samuel Marcos Ribeiro de Noronha, Silvana Aparecida Alves Correa de Noronha, Maria Del Carmen Garcia Molina Wolgien, Alexandre Jesus Barros, Clovis Ryiuchi Nakaie, Suma Imura Shimuta, Gil Facina, Ismael Dale Cotrim Guerreiro da Silva

Departamento de Biofísica, Universidade Federal de S?o Paulo, S?o Paulo, Brazil.
Laboratorio de Cirurgia Translacional, Departamento de Cirurgia, UNIFESP/EPM, S?o Paulo, Brazil.
Laboratório de Ginecologia Molecular, Universidade Federal de S?o Paulo, S?o Paulo, Brazil.

DOI: 10.4236/jct.2013.47A011                

Abstract

Breast cancer is the most common cancer among women. Angiotensin-(1 - 7) [Ang-(1 - 7)] has been correlated with cancer antiproliferative and apoptotic effects, similar properties of the human Chorionic Gonadotrofin (hCG). The aims of this work are to evaluate the role of Ang-(1 - 7) and of hCG in modulating the expression of Nuclear Receptors and Coregulators related genes in the tumorigenic breast cell line SK-BR3. Three experimental groups were created: control, hCG and hCG + Ang-(1 - 7). Cells were treated for 11 days and then had their RNA extracted. Samples were loaded into PCR Array plates containing 84 genes relate to Nuclear Receptors and Coregulators pathways. Gene expression data were used to construct canonical pathways (Metacore^TM). hCG and hCG + Ang-(1 - 7) treatments markedly modulate the expression of Nuclear Receptors and Coregulators related genes. hCG differentially expressed 17% of the genes, being 29% upregulated and 71% downregulated. Meanwhile, hCG + Ang-(1 - 7) changed the expression of 30% of the genes on the plate, among these genes 56% were upregulated and 44% downregulated. Among these differentially expressed genes, we highlight Esr1, Nr2f2, and Nr2f1, Esr1, Hdac5, and Nr4A1 (>4 fold). Finally MetaCore analysis based on Gene Ontology (GO) generated six networks for hCG and ten networks for the combined treatment. All generated networks are related to regulation of apoptosis or to Programmed Cell Death processes. In summary, our results herein demonstrate that the modulation of sexual hormones and of other nuclear factor genes expression might underlie the tumorigenic protection effect and the induction of cell differentiation caused by the hormones hCG and Ang-(1 - 7), especially in Cancer Stem Cells.

Keywords

Breast Stem Cancer Cells; SK-BR3; hCG; Angiotensin-(1 - 7)

Conflicts of Interest

The authors declare no conflicts of interest.

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