Establishment of gene diagnosis and therapy for Endometrial carcinoma.

子宫内膜癌基因诊断和治疗的建立。

• 批准号: 07457391
• 负责人: WAKE Norio
• 金额: $ 4.67万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457391/
• 关键词: Chromosome 1; Tumor suppressor gene; asingle chromosome transfer; Ras; Estrogen Receptor; Transcription factor; Endometrial Carcinoma; chromosomel; K-ras mutation; Genomic instability; Endometrial cancer

1. We made various fragments derived from a human chromosome 1 by high dose radiation, and transferred them into endometrial carcinoma cells via microcell fusion. The introduction of a whole chromosome 1 resulted in the morphological alteration followed by cell senescence. In addition, telomerase activity was also suppressed in the microcell hybrids containing a chromosome 1. Evaluation of cell morphology in addition to telomerase activity in the microcell hybrid clones containing various fragments form chromosome 1 disclosed that 1q11-q21 or q31-ter region of chromosome 1 was critical for the suppression of endometrial cell growth properties.2. We established the reconstituted cells expressing that mutant K-Ras protein constitutively. Enchanced expression of ER protein that has a function as a transcription factor was shown in this cell. We also established the reconstituted cells expressing both the wild type of K-Ras protein and ER protein. Long term culture in the presence of 10% calf serum transformed the cell that was analogous to the level in the mutant K-Ras expressing cells, was shown in this transformed cells. These implicate ER protein in Ras-mediated transformation.

1. 我们通过高剂量辐射制造了源自人类1号染色体的各种片段，并通过微细胞融合将它们转移到子宫内膜癌细胞中。整个 1 号染色体的引入导致形态改变，随后细胞衰老。此外，含有1号染色体的微细胞杂交体中端粒酶活性也受到抑制。对含有1号染色体各种片段的微细胞杂交体克隆中的细胞形态和端粒酶活性进行评估发现，1号染色体的1q11-q21或q31-ter区域对于抑制子宫内膜细胞生长特性至关重要。 2．我们建立了组成型表达突变 K-Ras 蛋白的重组细胞。该细胞中显示出具有转录因子功能的 ER 蛋白表达增强。我们还建立了表达野生型 K-Ras 蛋白和 ER 蛋白的重组细胞。在存在10%小牛血清的情况下长期培养转化的细胞与突变型K-Ras表达细胞中的水平类似，在该转化的细胞中显示。这些表明 ER 蛋白参与 Ras 介导的转化。

项目成果

Arima,T.,: "Malignant trophoblastic neoplasms with different modes of origin." Cancer Genet Cytogenet. 88. 5-15 (1995)

Arima,T.，：“具有不同起源模式的恶性滋养细胞肿瘤。”

Kato K: "The level of ER protein expression is increased in NIH3T3 cell transformed by oncogenic K-Ras 4B : Sex Steroid Hormone Action In in vitro culture syste." Churchill Living stone Japan. 31-40 (1996)

Kato K：“致癌 K-Ras 4B 转化的 NIH3T3 细胞中 ER 蛋白表达水平增加：体外培养系统中性类固醇激素的作用。”

Kato,K.,: "Endometriosis today" Analysis of danazol action.(in press),

Kato,K.，：“今天的子宫内膜异位症”达那唑作用分析。（正在印刷中），

Kato K: "Sex Steroid Hormone Action In in vitro culture system." The level of ER protein expression is increased in NIH3T3 cell transformed by oncogenic K-Ras 4B, 31-40 (1996)

Kato K：“性类固醇激素在体外培养系统中的作用。”

Koto, K.,: "The level of ER protein expression is increased in NIH3T3 cell transformed by oncogenic K-Ras 4B: Sex Steroid HOrmone Action In in vitro culture system." Churchill Living stone (Japan). (in press).

Koto, K.，：“在体外培养系统中，通过致癌 K-Ras 4B 转化的 NIH3T3 细胞中 ER 蛋白表达水平有所增加：性类固醇激素作用。”