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

甲状旁腺细胞生长调控及甲状旁腺腺瘤发生机制的分子研究

• 批准号: 11671095
• 负责人: SAKAGUCHI Kazushige
• 金额: $ 2.3万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671095/
• 关键词: parathyroid; tumor; oncogene; cDNA cloning; keratinocyte growth factor receptor; Yeast Two Hybrid; signal transduction; cDNA クローニング

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.

我们试图从甲状旁腺腺瘤的cDNA文库中系统地克隆癌基因，并对这些基因进行功能分析。角化细胞生长因子受体的同种型，其具有C-末端的选择性剪接形式，被分离，并发现在甲状旁腺腺瘤中表达，但在甲状旁腺癌或增生中不表达。两种可能性，变体C末端具有激活信号转导的功能或野生型C末端携带抑制信号转导的功能。为了阐明这些可能性，我们使用酵母双杂交系统来克隆可以与角质形成细胞生长因子受体的这些C末端部分结合的分子，这导致了几种分子的发现。我们现在正在研究这些克隆体的功能。

项目成果

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)

Kazushige Sakaguchi、Matthew V.Lorenzi、Hiroshi Matsushita 和 Toru Miki：“通过甲状旁腺腺瘤组织的表达克隆鉴定角化细胞生长因子受体的新型激活形式。”癌基因。

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)

Kazushige Sakaguchi、Matthew V.Lorenzi、Donald P.Bottaro 和 Toru Miki：“FGF 受体 2 的酸性结构域和第一个免疫球蛋白样环通过糖胺聚糖修饰调节下游信号传导。”Mol.Cell.Biol.. 19. 6754-

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)

Kazushige Sakaguchi 等人：“成纤维细胞生长因子受体 2 的酸性结构域和第一个免疫球蛋白样环通过糖胺聚糖修饰调节下游信号”分子和细胞生物学 19·10（1999）。

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)

Kazushige Sakaguchi 等人：“通过甲状旁腺腺瘤的表达克隆鉴定一种新型激活形式的角质形成细胞生长因子受体”癌基因。

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)

Kazushige Sakaguchi、Matthew V.Lorenzi Hiroshi Matsushita、Toru Miki：“通过甲状旁腺腺瘤组织的表达克隆鉴定角化细胞生长因子受体的新型激活形式”癌基因。