title: Heat shock protein 70-2 (HSP70-2) overexpression in breast cancer.
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.
authors.affiliation: Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India.
authors.forename: Nirmala
authors.initials: N
authors.lastname: Jagadish
authors.affiliation: Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India.
authors.forename: Sumit
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India.
authors.forename: Namita
authors.initials: N
authors.lastname: Gupta
authors.affiliation: Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India.
authors.forename: Rukhsar
authors.initials: R
authors.lastname: Fatima
authors.affiliation: Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India.
authors.forename: Sonika
authors.initials: S
authors.lastname: Devi
authors.affiliation: Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India.
authors.forename: Vikash
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Suri
authors.affiliation: All India Institute of Medical Sciences, Institute of Rotary Cancer Hospital, New Delhi, 110029, India.
authors.forename: Rajive
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Mahatma Gandhi Medical College and Hospital, Jaipur, 302022, India.
authors.forename: Vitusha
authors.initials: V
authors.lastname: Suri
authors.affiliation: Mahatma Gandhi Medical College and Hospital, Jaipur, 302022, India.
authors.forename: Trilok Chand
authors.initials: TC
authors.lastname: Sadasukhi
authors.affiliation: Department of Pathology, NMC Imaging and Diagnostic Centre, Vidyasagar Institute of Mental Health and Neuro-Sciences, New Delhi, 110065, India.
authors.forename: Anju
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Centre for Advanced Studies, Department of Zoology, University of Rajasthan, Jaipur, 302 004, India.
authors.forename: Abdul S
authors.initials: AS
authors.lastname: Ansari
authors.affiliation: Centre for Advanced Studies, Department of Zoology, University of Rajasthan, Jaipur, 302 004, India.
authors.forename: Nirmal Kumar
authors.initials: NK
authors.lastname: Lohiya
authors.affiliation: Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India. anil@nii.res.in.
authors.forename: Anil
authors.initials: A
authors.lastname: Suri
keywords: Apoptosis; Breast cancer; Gene silencing; HSP70-2; Tumor growth