TITLE:
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
AUTHORS:
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
KEYWORDS:
Breast Stem Cancer Cells; SK-BR3; hCG; Angiotensin-(1 - 7)
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.7A,
July
23,
2013
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.