title: Heat shock protein 70-2 (HSP70-2) is a novel therapeutic target for colorectal cancer and is associated with tumor growth.
abstract: Colorectal cancer (CRC) is the third leading cause of cancer related deaths worldwide both in men and women. Our recent studies have indicated an association of heat shock protein 70-2 (HSP70-2) with bladder urothelial carcinoma. In the present study, we investigated the association of HSP70-2 with various malignant properties of colorectal cancer cells and clinic-pathological features of CRC in clinical specimens.
  
  
  
  HSP70-2 mRNA and protein was investigated expression by RT-PCR, immunohistochemistry, immunofluorescence, flow cytometry and Western blotting in CRC clinical specimens and COLO205 and HCT116 cell lines. Plasmid-based gene silencing approach was employed to study the association of HSP70-2 with various malignant properties of COLO205 and HCT116 cells in in vitro and with tumor progression in in vivo COLO205 human xenograft mice model.
  
  
  
  HSP70-2 expression was detected in 78 % of CRC patients irrespective of various stages and grades by RT-PCR and IHC. Our analysis further revealed that HSP70-2 expression was detected in both COLO205 and HCT116 cell lines. Ablation of HSP70-2 expression resulted in reduced cellular growth, colony forming ability, migratory and invasive ability of CRC cells. In addition, ablation of HSP70-2 expression showed significant reduction in tumor growth in COLO205 human xenograft in in vivo mouse model.
  
  
  
  Collectively, our results indicate that HSP70-2 is associated with CRC clinical specimens. In addition, down regulation of HSP70-2 expression reduces cellular proliferation and tumor growth indicating that HSP70-2 may be a potential therapeutic target for CRC 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: Deepak
authors.initials: D
authors.lastname: Parashar
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: Sumit
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Suri
authors.affiliation: Institute of Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Rajive
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Urology, Mahatma Gandhi Medical College and Hospital, Rajasthan, 302022, India.
authors.forename: Vitusha
authors.initials: V
authors.lastname: Suri
authors.affiliation: Department of Urology, Mahatma Gandhi Medical College and Hospital, Rajasthan, 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
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016513:Mice, SCID; D034622:RNA Interference; D000067492:RNAi Therapeutics / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D018840:HSP70 Heat-Shock Proteins; C525621:HSPA1B protein, human
keywords: Cancer testis antigen; Gene silencing; HSP70-2; Therapeutic target