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Jagadish N, Agarwal S, Gupta N, et al. Heat shock protein 70-2 (HSP70-2) overexpression in breast cancer. J Exp Clin Cancer Res. 2016;35(1):150doi: 10.1186/s13046-016-0425-9.
Jagadish, N., Agarwal, S., Gupta, N., Fatima, R., Devi, S., Kumar, V., Suri, V., Kumar, R., Suri, V., Sadasukhi, T. C., Gupta, A., Ansari, A. S., Lohiya, N. K., & Suri, A. (2016). Heat shock protein 70-2 (HSP70-2) overexpression in breast cancer. Journal of experimental & clinical cancer research : CR, 35(1), 150. https://doi.org/10.1186/s13046-016-0425-9
Jagadish, Nirmala, et al. "Heat shock protein 70-2 (HSP70-2) overexpression in breast cancer." Journal of experimental & clinical cancer research : CR vol. 35,1 (2016): 150. doi: https://doi.org/10.1186/s13046-016-0425-9
Jagadish N, Agarwal S, Gupta N, Fatima R, Devi S, Kumar V, Suri V, Kumar R, Suri V, Sadasukhi TC, Gupta A, Ansari AS, Lohiya NK, Suri A. Heat shock protein 70-2 (HSP70-2) overexpression in breast cancer. J Exp Clin Cancer Res. 2016 Sep 22;35(1):150. doi: 10.1186/s13046-016-0425-9. PMID: 27658496; PMCID: PMC5034467.
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J Exp Clin Cancer Res. 2016 Sep 22;35(1):150. doi: 10.1186/s13046-016-0425-9.

Heat shock protein 70-2 (HSP70-2) overexpression in breast cancer.

Journal of experimental & clinical cancer research : CR

Nirmala Jagadish, Sumit Agarwal, Namita Gupta, Rukhsar Fatima, Sonika Devi, Vikash Kumar, Vaishali Suri, Rajive Kumar, Vitusha Suri, Trilok Chand Sadasukhi, Anju Gupta, Abdul S Ansari, Nirmal Kumar Lohiya, Anil Suri

Affiliations

  1. Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India.
  2. Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
  3. All India Institute of Medical Sciences, Institute of Rotary Cancer Hospital, New Delhi, 110029, India.
  4. Mahatma Gandhi Medical College and Hospital, Jaipur, 302022, India.
  5. Department of Pathology, NMC Imaging and Diagnostic Centre, Vidyasagar Institute of Mental Health and Neuro-Sciences, New Delhi, 110065, India.
  6. Centre for Advanced Studies, Department of Zoology, University of Rajasthan, Jaipur, 302 004, India.
  7. Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India. [email protected].

PMID: 27658496 PMCID: PMC5034467 DOI: 10.1186/s13046-016-0425-9

Abstract

BACKGROUND: Breast 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.

METHODS: HSP70-2 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.

RESULTS: HSP70-2 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.

CONCLUSIONS: HSP70-2 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.

Keywords: Apoptosis; Breast cancer; Gene silencing; HSP70-2; Tumor growth

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