Proteomic analysis of molecular-targeted therapy against KGFR of salivary gland carcinomas

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18592184
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hiroshima University
• Principal Investigator: TORATANI Shigeaki Hiroshima University, Hiroshima University Hospital, Associate Professor (90172220)
• Co-Investigator(Kenkyū-buntansha): OKAMOTO Tetsuji Hiroshima University, Graduate School of Biomedical Sciences, Professor (00169153)
• Project Period (FY): 2006 – 2007
• Keywords: KGFR / carcinoma of salivary gland / differentiation / proteomic analysis / FGF

Research Abstract

KGF, one of fibroblast growth factor receptor, is a receptor gene of KGF/FGF-7. We clarified salivary gland tumors accompany the abnormal expression or over-expression of FGF-2 in the process of malignant alteration, furthermore, KGFR gene expression disappeared and FGFR1-IIIc gene, receptor gene of FGF-2 without expression in salivary gland epithelium usually, increase as the enlarging malignancy.
In this study, gene expressions were analyzed systematically and exhaustively for salivary gland carcinoma cells transfected wild-type KGFR, gene and control carcinoma cells. And we analyzed not only construction or change in function of oncogene and tumor suppressor gene products but also expression level of interfaced proteins and modified change after translation. FGF2-FGFR1-IIIc system was blocked through inhibition of FGFR1-IIIc expression using shRNA expression vector. The proliferation potency of cells transferred FGFR1-IIIc siRNA decreased. The gene and protein groups by related cell differentiation and apoptosis inducted with manipulation of FGF-FGFR signal were analyzes by DNA micro array and proteome system.
In the results, about 900 gene expressions of salivary gland carcinoma transferred wild type KGFR gene were increased. Although about 400 gene expressions were decreased. Variation of gene expressions related apoptosis, carcinogenesis, cell cycle and molecular transducer were recognized. Compared gene expression of cells transfected KGFR gene with cells transfferd FGFR1 siRNA, above 50 genes were overlapped Next proteomic analysis of protein group interlocking FGFR was performed. Above 80 protein spots varied twice were detected. In contrast, above 100 protein spots were changed by transfection of FGFR1 siRNA.

Research Products

• [Journal Article] Immunohistochemical expression of heparin-binding protein17/fib roblast growth factor-binding protein-1(HBp17/FGFRBP-1) as an angiogenic factor in head and neck tumorigenesis. (2007)
  • Author(s): Begum S, Zhang Y, Shintani T, Toratani S, Sato J D, Okamoto T.
  • Journal Title: Oncology Report 17 Pages: 591-596
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Immunohistochemical expression of heparin-binding protein 17/fibroblast growth factor-binding protein (HBpl7/FGFBP-1)as an angiogenic factor in head and neck tumorigenesis (2007)
  • Author(s): Begum, S., Zhang, Y., Shintani, T., Toratani, S., Sato, JD., Tetsuji Okamoto
  • Journal Title: Oncol Rep. 17(3) Pages: 591-596
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Developmental Signaling Disorders in Craniofacial Anomalies and Cancers (2006)
  • Author(s): Zhang, Y., Whang, H., Kitamura, N., Toratani, S., Okamoto, T., et al.
  • Journal Title: Oral Science International, 3(2). 3 Pages: 56-63
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Developmental Signaling Disorders in Craniofacial Anomalies and Cancers (2006)
  • Author(s): Zhang, Y., Whang, H., Kitamura, N., Toratani, S., Okamoto, T., et al.
  • Journal Title: Oral Science International 3(2) Pages: 56-63
  • Description: 「研究成果報告書概要(欧文)」より