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Function of parafibromin inhibiting parathyroid tumorigenesis

甲状纤维蛋白抑制甲状旁腺肿瘤发生的作用

基本信息

批准号：
17590963
负责人：
YOSHIMOTO Katsuhiko
金额：
$ 2.24万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590963/
关键词：
parathyroid hereditary tumor endocrine oncogene tumor suppressor gene 癌抑制遺伝子癌遺伝子

项目摘要

Germline mutations of HRPT2 were found in 2 of 11 FIHP families and 1 of 2 HPT-JT families. One FIHP family with parathyroid carcinoma and atypical adenomas, and another FIHP family with cystic parathyroid adenoma had novel frameshift mutations of 518-521del and 62-66del, respectively. In a patient with HPT-JT, a de novo germline mutation of 39delC was detected. Novel somatic HRPT2 mutations of 70-73del and 95-102del were found in 2 of 5 parathyroid tumors in a family with 518-521 del mutation. Biallelic inactivation of HRPT2 by a combination of germline mutation and somatic mutation was confirmed in parathyroid tumors. The finding that 2 families diagnosed with FIHP carried HRPT2 mutations suggests that they have occult HPT-JT.Parafibromin is a 531-amino acid protein product encoded by HRPT2, a putative tumor suppressor gene recently implicated in the autosomal dominant hyperparathyroidism-jaw tumor familial cancer syndrome and sporadic parathyroid carcinoma. To investigate effects of parafibromin overexpression on cell proliferation, we performed cell proliferation assay in four different cell lines. Transient parafibromin overexpression inhibited cell growth in HEK293 and NIH3T3 cells, whereas enhanced cell growth in SV40 large T antigen expressing-cell lines such as 293FT and COS7 cells. In 293FT cells, the parafibromin was found to interact with SV40 large T antigen and overexpression of parafibromin promoted entry into S phase, implying that interaction between parafibromin and SV40 large T antigen enhanced cell cycle progression. Based on these we conclude that tumor suppressor protein, parafibromin, acts a positive regulator of cell growth such as oncoproteins at the presence of SV40 large T antigen.

在11个FIHP家系中有2个发生HRPT 2基因突变，在2个HPT-JT家系中有1个发生HRPT 2基因突变。一个甲状旁腺癌和非典型腺瘤的FIHP家族和另一个甲状旁腺囊性腺瘤的FIHP家族分别有518- 521 del和62- 66 del的新移码突变。在HPT-JT患者中，检测到39 delC的从头生殖系突变。在一个有518-521 del突变的甲状旁腺肿瘤家系的5例甲状旁腺肿瘤中，2例发现了新的HRPT 2体细胞突变70- 73 del和95- 102 del。在甲状旁腺肿瘤中，通过生殖系突变和体细胞突变的组合证实了HRPT 2的双等位基因失活。2个FIHP家系均携带HRPT 2突变，提示其为隐匿性HPT JT。副纤维蛋白酶是由HRPT 2编码的一个531氨基酸的蛋白产物，是一种肿瘤抑制基因，与常染色体显性遗传性甲状旁腺增生-颌骨肿瘤家族性癌症综合征和散发性甲状旁腺癌有关。为了研究副纤维蛋白过表达对细胞增殖的影响，我们在四种不同的细胞系中进行细胞增殖测定。瞬时过表达parafibromin抑制HEK 293和NIH 3 T3细胞的细胞生长，而增强SV 40大T抗原表达细胞系如293 FT和COS 7细胞的细胞生长。在293 FT细胞中，发现parafibromin与SV 40大T抗原相互作用，并且parafibromin的过表达促进进入S期，这意味着parafibromin与SV 40大T抗原之间的相互作用促进细胞周期进程。基于这些，我们得出结论，肿瘤抑制蛋白，parafibromin，作为一个积极的调节细胞生长，如癌蛋白在SV 40大T抗原的存在。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Somatic mutations of the CTNNBI gene in cribriform-morular variant of papillary thyroid carcinoma

甲状腺乳头状癌筛状-桑叶变异体 CTNNBI 基因的体细胞突变

DOI：
发表时间：
期刊：
Recent Advances in Thyroid Cancer Research (In press)
影响因子：
0
作者：
Yamazaki K;Suzuki K;Emiko Yamada E;Yamada T;Takeshita F;Matsumoto M;Mitsuhashi T;Obara T;Takano K;Sato K;Iwata T et al.;柴田洋孝;Palona I;Yoshimoto K et al.
通讯作者：
Yoshimoto K et al.

Molecular cloning of a murine glycerol-3-phosphate acyltransferase-like protein 1 (xGPATI)

鼠类 3-磷酸甘油酰基转移酶样蛋白 1 (xGPATI) 的分子克隆