Molecular studies on the regulation of parathyroid cell growth and the mechanisms of parathyroid adenoma development

• Project/Area Number: 11671095
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Wakayama Medical University
• Principal Investigator: SAKAGUCHI Kazushige Wakayama Medical University Professor, 付置研究所, 教授 (60178548)
• Co-Investigator(Kenkyū-buntansha): YOKOTE Hideyuki Wakayama Med Univ, Mol Med, Assistant Prof, 付置研究所, 助手 (60316122) ; NAKAMURA Masayuki Wakayama Med Univ, Mol Med, Assistant Prof, 付置研究所, 助手 (40145917)
• Project Period (FY): 1999 – 2000
• Project Status: Completed (Fiscal Year 2000)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: parathyroid / tumor / oncogene / cDNA cloning / keratinocyte growth factor receptor / Yeast Two Hybrid / signal transduction / cDNA クローニング

Research Abstract

We have attempted systematical expression cloning of oncogenes from a cDNA library derived from a parathyroid adenoma, and functional analysis of these genes. An isoform of keratinocyte growth factor receptor, which has an alternatively spliced form of C-terminus, was isolated, and found to be expressed in parathyroid adenoma, but not in parathyroid cancer or hyperplasia. Two possibilities, the variant C terminus having functions of activating the signal transduction or the wild-type C terminus carrying the functions of inhibiting the signaling. To clarify these possibilities, we used the Yeast Two Hybrid system to clone the molecules that can bind to these C terminus portion of the keratinocyte growth factor receptor, which leads to the discovery of several molecules. We are now in the middle of characterizing the function of these clones.

Research Products

• [Publications] Kazushige Sakaguchi et al.: "Identification of a novel activated form of keratinocyte growth factor receptor by expression cloning from parathyroid adenoma"Oncogene. 18. 5497-5505 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kazushige Sakaguchi et al.: "The acidic domain and first immunoglobulin-like loop of fibroblast growth factor receptor 2 modulate downstream signaling through glycosaminoglycan modification"Molecular and Cellular Biology. 19・10. 6754-6764 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kazushige Sakaguchi, Matthew V.Lorenzi, Hiroshi Matsushita, and Toru Miki: "Identification of a novel activated form of the keratinocyte growth factor receptor by expression cloning from parathyroid adenoma tissue."Oncogene. 18. 5497-5505 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kazushige Sakaguchi, Matthew V.Lorenzi, Donald P.Bottaro and Toru Miki: "The acidic domain and first immunoglobulin-like loop of FGF receptor-2 modulate downstream signaling through glycosaminoglycan modification."Mol.Cell.Biol.. 19. 6754-6764 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kazushige Sakaguchi et al.: "Identification of a novel activated form of keratinocyte growth factor receptor by expression cloning from parathyroid adenoma"Oncogene. 18. 5497-5505 (1999)
• [Publications] Kazushige Sakaguchi,Matthew V.Lorenzi Hiroshi Matsushita,Toru Miki: "Identification of a novel activated form of the Keratinocyte growth factor receptor by expression cloning from parathyroid adenoma tissue"Oncogene. 18. 5497-5505 (1999)