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Journal of Experimental and Clinical Cancer Research

, 35:150

First Online: 22 September 2016Received: 19 June 2016Accepted: 13 September 2016DOI: 10.1186-s13046-016-0425-9

Cite this article as: Jagadish, N., Agarwal, S., Gupta, N. et al. J Exp Clin Cancer Res 2016 35: 150. doi:10.1186-s13046-016-0425-9

Abstract

BackgroundBreast cancer is one of the leading cause of cancer-related deaths in women worldwide and increasing rapidly in developing countries. In the present study, we investigated the potential role and association of HSP70-2 with breast cancer.

MethodsHSP70-2 expression was examined in 154 tumor and 103 adjacent non-cancerous tissue ANCT specimens and breast cancer cell lines MCF7, BT-474, SK-BR-3 and MDA-MB-231 by RT-PCR, quantitative-PCR, immunohistochemistry, Western blotting, flow cytometry and indirect immunofluorescence. Plasmid driven short hairpin RNA approach was employed to validate the role of HSP70-2 in cellular proliferation, senescence, migration, invasion and tumor growth. Further, we studied the effect of HSP70-2 protein ablation on signaling cascades involved in apoptosis, cell cycle and Epithelial-Mesenchymal-Transition both in culture as well as in-vivo human breast xenograft mouse model.

ResultsHSP70-2 expression was detected in majority of breast cancer patients 83 % irrespective of various histotypes, stages and grades. HSP70-2 expression was also observed in all breast cancer cells BT-474, MCF7, MDA-MB-231 and SK-BR-3 used in this study. Depletion of HSP70-2 in MDA-MB-231 and MCF7 cells resulted in a significant reduction in cellular growth, motility, onset of apoptosis, senescence, cell cycle arrest as well as reduction of tumor growth in the xenograft model. At molecular level, down-regulation of HSP70-2 resulted in reduced expression of cyclins, cyclin dependent kinases, anti-apoptotic molecules and mesenchymal markers and enhanced expression of CDK inhibitors, caspases, pro-apoptotic molecules and epithelial markers.

ConclusionsHSP70-2 is over expressed in breast cancer patients and was involved in malignant properties of breast cancer. This suggests HSP70-2 may be potential candidate molecule for development of better breast cancer treatment.

KeywordsHSP70-2 Breast cancer Gene silencing Apoptosis Tumor growth Electronic supplementary materialThe online version of this article doi:10.1186-s13046-016-0425-9 contains supplementary material, which is available to authorized users.

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Autor: Nirmala Jagadish - Sumit Agarwal - Namita Gupta - Rukhsar Fatima - Sonika Devi - Vikash Kumar - Vaishali Suri - Rajive Kum

Fuente: https://link.springer.com/



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