Share This Article:

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

Abstract Full-Text HTML Download Download as PDF (Size:721KB) PP. 70-74
DOI: 10.4236/jct.2013.47A011    3,931 Downloads   5,277 Views   Citations

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.

Conflicts of Interest

The authors declare no conflicts of interest.

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. 7A, 2013, pp. 70-74. doi: 10.4236/jct.2013.47A011.

References

[1] American Cancer Society, “Cancer Facts & Figures 2012,” American Cancer Society, Atlanta, 2012.
[2] T. Kosaka, A. Miyajima, S. Shirotake, E. Kikuchi and M. Oya, “Phosphorylated Akt Up-Regulates Angiotensin II Type-1 Receptor Expression in Castration Resistant Prostate Cancer,” Vol. 71, No. 15, Prostate, 2011, pp. 15010-1517.
[3] N. Queisser, P. I. Oteiza, H. Stopper, R. G. Oli and N. Schupp, “Aldosterone Induces Oxidative Stress, Oxidative DNA Damage and NF-κB-Activation in Kidney Tubule Cells,” Molecular Carcinogenesis, Vol. 50, No. 2, 2011, pp. 123-135. doi:10.1002/mc.20710
[4] K. Hoshino, H. Ishiguro, J. I. Teranishi, et al., “Regulation of Androgen Receptor Expression through Angiotensin II Type 1 Receptor in Prostate Cancer Cells,” Prostate, Vol. 71, No. 9, 2010, pp. 964-975. doi:10.1002/pros.21312
[5] K. Okamoto, H. Tajima and T. Ohta, et al., “The Role of Renin-Angiotensin System Independent Angiotensin II Production in Progression and Fibrosis of Intrahepatic Cholangiocarcinoma,” Japanese Journal of Cancer and Chemotherapy, Vol. 37, No. 12, 2010, pp. 2231-2233.
[6] M. Fujita, I. Hayashi, S. Yamashina, M. Itoman and M. Majima, “Blockade of Angiotensin AT1a Receptor Signaling Reduces Tumor Growth, Angiogenesis, and Metastasis,” Biochemical and Biophysical Research Communications, Vol. 294, No. 2, 2002, pp. 441-447. doi:10.1016/S0006-291X(02)00496-5
[7] S. Greco, A. Muscella, M. G. Elia, et al., “Angiotensin II Activates Extracellular Signal Regulated Kinases via Protein Kinase C and Epidermal Growth Factor Receptor in Breast Cancer Cells,” Journal of Cellular Physiology, Vol. 196, No. 2, 2003, pp. 370-377. doi:10.1002/jcp.10313
[8] S. A. Alves Correa, S. M. Ribeiro de Noronha, N. C. Nogueira-de-Souza, et al., “Association between the Angiotensin-Converting Enzyme (Insertion/Deletion) and Angiotensin II Type 1 Receptor (A1166C) Polymorphisms and Breast Cancer among Brazilian Women,” Journal of the Renin-Angiotensin-Aldosterone System, Vol. 10, No. 1, 2009, pp. 51-58. doi:10.1177/1470320309102317
[9] A. P. Mendizábal-Ruiz, J. A. Morales, X. Castro Marti Nez, et al., “RAS Polymorphisms in Cancerous and Benign Breast Tissue,” Journal of the Renin-AngiotensinAldosterone System, Vol. 12, No. 2, 2011, pp. 85-92. doi:10.1177/1470320310383735
[10] S. Namazi, A. Monabati, S. Ardeshir-Rouhani-Fard and N. Azarpira, “Association of Angiotensin I Converting Enzyme (Insertion/Deletion) and Angiotensin II Type 1 Receptor (A1166C) Polymorphisms with Breast Cancer Prognostic Factors in Iranian Population,” Molecular Carcinogenesis, Vol. 49, No. 12, 2010, pp. 1022-1030. doi:10.1002/mc.20685
[11] M. del Pilar Carrera, M. J. Ramírez-Expósito, M. D. Mayas, M. J. García and J. M. Martínez-Martos, “Mammary Renin-Angiotensin System-Regulating Aminopeptidase Activities Are Modified in Rats with Breast Cancer,” Tumor Biology, Vol. 31, No. 6, 2010, pp. 583-588. doi:10.1007/s13277-010-0072-2
[12] B. Krishnan, T. L. Smith, P. Dubey, et al., “Angiotensin(1-7) Attenuates Metastatic Prostate Cancer and Reduces Osteoclastogenesis,” Prostate, Vol. 73, No. 1, 2013, pp. 71-82. doi:10.1002/pros.22542
[13] D. R. Soto-Pantoja, J. Menon, P. E. Gallagher and E.A. Tallant, “Angiotensin-(1-7) Inhibits Tumor Angiogenesis in Human Lung Cancer Xenografts with a Reduction in Vascular Endothelial Growth Factor,” Molecular Cancer Therapeutics, Vol. 8, No. 6, 2009, pp. 1676-1683. doi:10.1158/1535-7163.MCT-09-0161
[14] P. Economopoulou, V. G. Kaklamani and K. Siziopikou, “The Role of Cancer Stem Cells in Breast Cancer Initiation and Progression: Potential Cancer Stem CellDirected Therapies,” Oncologist, Vol. 17, No. 11, 2012, pp. 1394-1401. doi:10.1634/theoncologist.2012-0163
[15] S. M. R. Noronha, S. A. A. Correa-Noronha, I. H. Russo, R. L. de Cicco, J. Santucci-Pereira and J. Russo, “Human Chorionic Gonadotropin and a 15 Amino Acid hCG Fragment of the Hormone Induce Downregulation of the Cytokine IL-8 Receptor in Normal Breast Epithelial Cells,” Hormone Molecular Biology and Clinical Investigation, Vol. 6, No. 3, pp. 241-245.
[16] C. A. Santos, “Papel da Angiotensina II e Angiotensina-(1-7) na Proliferacao E Progressao do Cancer de Mama,” MsC. Thesis, Universidade Federal de S?o Paulo (UNIFESPEPM), S?o Paulo, 2013.
[17] ESR1, “Estrogen Receptor 1 [Homo sapiens (Human)]; Gene ID: 2099,” 2013. http://www.ncbi.nlm. nih.gov/gene/2099
[18] N. Hevir, N. Trost, N. Debeljak and T. L. Rizner, “Expression of Estrogen and Progesterone Receptors and Estrogen Metabolizing Enzymes in Different Breast Cancer Cell Lines,” Chemico-Biological Interactions, Vol. 191, No. 1-3, 2011, pp. 206-216. doi:10.1016/j.cbi.2010.12.013
[19] J. Qin, X. Chen, X. Xie, M. J. Tsai and S. Y. Tsai, “COUP-TFII Regulates Tumor Growth and Metastasis by Modulating Tumor Angiogenesis,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 8, 2010, pp. 3687-3692. doi:10.1073/pnas.0914619107
[20] E. Moré, T. Fellner, H. Doppelmayr, et al., “Activation of the MAP Kinase Pathway Induces Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) Expression in Human Breast Cancer Cell Lines,” Journal of Endocrinology, Vol. 176, No. 1, 2003, pp. 83-94. doi:10.1677/joe.0.1760083
[21] P. Peixoto, V. Castronovo, N. Matheus, et al., “HDAC5 Is Required for Maintenance of Pericentric Heterochromatin, and Controls Cell-Cycle Progression and Survival of Human Cancer Cells,” Cell Death & Differentiation, Vol. 19, No. 7, 2012, pp. 1239-1252. doi:10.1038/cdd.2012.3
[22] H. Kocdor, M. A. Kocdor, J. Russo, et al., “Human Chorionic Gonadotropin (hCG) Prevents the Transformed Phenotypes Induced by 17 Beta-Estradiol in Human Breast Epithelial Cells,” Cell Biology International, Vol. 33, No. 11, 2009, pp. 1135-1143. doi:10.1016/j.cellbi.2009.07.002
[23] K. L. Cook, L. J. Metheny-Barlow, E. A. Tallant, et al., “Angiotensin-(1-7) Reduces Fibrosis in Orthotopic Breast Tumors,” Cancer Research, Vol. 70, No. 21, 2010, pp. 8319-8328. doi:10.1158/0008-5472.CAN-10-1136

  
comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.