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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0425-9) contains supplementary material, which is available to authorized users.
Highlights
Breast cancer is one of the leading cause of cancer-related deaths in women worldwide and increasing rapidly in developing countries
HSP70-2 is overexpressed in clinical samples of breast tumors The expression of HSP70-2 mRNA and protein was examined in breast clinical cancer specimens by qRT-PCR and IHC respectively
HSP70-2 is over-expressed in breast cancer cell lines Since breast tumor samples showed overexpression of HSP70-2 mRNA as well as protein, we examined its expression in four different breast cancer cell lines viz., BT-474, MCF7, MDA-MB-231 and SK-BR-3
Summary
Breast cancer is one of the leading cause of cancer-related deaths in women worldwide and increasing rapidly in developing countries. We investigated the potential role and association of HSP70-2 with breast cancer. Breast cancer is the second leading cause of cancer related deaths among women worldwide [1]. Breast cancers are mostly adenocarcinomas which include invasive type such as infiltrating ductal carcinoma (IDC) and non-invasive type, Ductal Carcinoma in-situ (DCIS) [2]. IDC is the most common subtype of breast cancer accounting for 75–80 % of all the cases diagnosed [3]. Heat shock family of proteins (HSPs) is proposed to play pivotal role in breast tumor development owing to their intrinsic molecular chaperone properties [5]. Few of the HSPs have been reported in breast cancer which includes
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