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

doi:10.4236/jct.2013.47A011

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

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 (MetacoreTM). 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)

Cite this paper: I. Neto, S. Noronha, S. Noronha, M. Wolgien, A. Barros, C. Nakaie, S. Shimuta, G. Facina and I. Silva, "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," Journal of Cancer Therapy, Vol. 4 No. 7, 2013, pp. 70-74. doi: 10.4236/jct.2013.47A011.

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