Introduction: Renin Angiotensin System (RAS) components are not only related to breast cancer but also to other cancer types. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous 7-amino acid peptide hormone of the renin-angiotensin system that has antiproliferative properties. The aim of this work is to analyze the action of Ang-(1-7) treatment in MCF-10F (normal) and in SKBR3 (tumoral) epithelial breast cells in their capacity to be droven to apoptosis, and also to assess the expression of the membrane receptors CD24 and CD44 in these cells. Methods: We used the SA Biosciences Human Apoptosis RT*2 Profiler PCR Array profiles to analyze the expression of 84 key genes involved in programmed cell death. Furthermore a flow cytometer (GUAVA) was used for quantification of the membrane proteins CD24 and CD44 in the MCF10F and in the SKBR3 breast cells after 24 hours of Angiotensin 1-7 stimulation. Results: Flow cytometric analysis using MCF10F cells showed that a 24h Ang1-7 stimulation period down regulates CD24 gene expression (about 43%) and it up regulates CD44 gene expression (about 16%). On the other hand there was no difference in the expression of both CD24 and CD44 proteins after Ang1-7 stimulation in SKBR3 tumoral cells. Furthermore, after the gene expression analysis by PCR Array, we found differential expression in MCF10F cells after Ang 1-7 treatment and we observed that the genes had their expression changed about 30% (2.1 to 514 fold increases) and 11% (2.6 to 3.8 fold decreases), respectively on a panel of 84 genes related to apoptosis. For SKBR3 cells, we found that the genes were altered in about 5.9% (2.6 to 5.4 fold increases) and 12% (2.1 to 3.3 fold decreases), respectively. Conclusion: Ang 1-7 appears to modulate the expression of membrane proteins CD24 and CD44 in MCF10F cells, also this hormone seems to induce apoptosis by inducing the expression of apoptosis related genes, such as, Abl1, Akt, Bax, Bcl2 (fold change, 3, 12, 6, and 6, respectively). Another important gene is the Hrk (harakiri, BCL2 interacting protein), that regulates apoptosis through interaction with death-repressor proteins Bcl-2 and Bcl-X(L), it displayed a fold change of 514. On the other hand in SKBR3 cells, comprised almost entirely by mammary stem cells, we found no regulation of CD24 and CD44 proteins by Ang1-7. Moreover, it was observed a very low differential expression in the genes related to the apoptosis pathway in these cells. However, the peptide Ang 1-7 seems to act preferentially in differentiated cells of the normal breast epithelium. Financial Support: FAPESP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3031. doi:1538-7445.AM2012-3031
Background: Many different types of cancer (renal, lung, colorectal, prostate, uterus, breast and pancreatic) have already been associated to polymorphisms of the Renin Angiotensin System (RAS) genes. Angiotensin II (Ang II) is a vasoconstrictor, a mitogen and a angiogenic factor, whereas the angiotensin-(1-7) [Ang-(1-7)] has vasodilator, antiproliferative and anti-angiogenic properties. Classically, Ang II and Ang-(1-7) exert their effects through the AGTR 1-2 and the MAS1 oncogene receptors respectively. The MAS1 receptor expression is associated to lung cancer and the hormone Ang-(1-7) inhibits proliferation in these neoplasias. Moreover, some studies have correlated the MAS1 receptor gene expression to breast cancer. To further test the hypothesis that Ang II and Ang-(1-7) participate in breast carcinogenesis through AGTR2 and MAS1 oncogene receptors respectivelly, we assessed genetic polymorphisms in the 5′-region of the AGTR2 gene (T1247G and A5235G) and in the MAS1 oncogene (C647T) in two groups: breast cancer patients and normal women and their possible associations to breast cancer among Brazilian women. Methods: The genotyping assay was performed through the Custom TaqMan SNP Genotyping assays, probes and primers Assay-by-Design were used for the end-point collection qPCR human SNPs genotyping. Genomic DNA samples were extracted from blood cells of patients with (case) or without breast cancer (control), aged between 26 and 90 years. In the polymorphism T1247G, 428 samples were processed: 263 cases and 165 controls; 429 samples for polymorphism A5235G: 257 cases and 172 controls and 429 samples in polymorphism C647T: 269 cases and 167 controls. Results: The following distribution of genotypes (%)were obtained for the three polymorphisms: T1247G - TT, TG, GG = 84, 13, 03 in case and 81, 18, 1 in control (p = 0,0025); A5235G - AA, AG, GG = 21, 44, 35 in case and 20, 27, 35 in control (p = 0,36); C647T - CC, CT, TT = 64.0, 0.4, 35.6 in case and 52.0, 0.6, 47.4 in control (p = 0,039). Therefore, T1247G and C647T polymorphisms are associated with breast cancer. Conclusions: Our results suggest an association between T1247G AGTR2 and C647T MAS1 oncogene polymorphisms with breast cancer in the Brazilian population. Both polymorphisms are found in the promoter region of these genes, making of these regions possible targets to change the binding of transcription factors that will eventually transcribe these genes and might result in a different cellular behavior when exposed to the same agonist molecule. This being the case, the T1247G and C647T are possible targets for assessing breast cancer risk, while the A5235G is not. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2598. doi:1538-7445.AM2012-2598
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.