Determination of full-length cDNA and genomic structure of the tumor suppressor gene candidates in lung cancer and screening for their mutations

肺癌候选抑癌基因全长cDNA和基因组结构的测定及突变筛查

• 批准号: 10470151
• 负责人: KUDOH Shoji
• 金额: $ 6.34万
• 依托单位: NIPPON MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470151/
• 关键词: Insulin-like growth factor 2 receptor; Genomic structure; PTEN; MMAC1; PTH2; allelic loss; hMAD2; insulin-like growth factor 2 Receptor; MMAC1; hMAD2; Insulin-like qrowth factor 2 Receptor

We conducted the structural analysis of the tumor suppressor candidates, Insulin-like growth factor 2 receptor (IGF2R), PTEN/MMAC1, its homologies, Hbub1, and Hmad2 gene. We also performed their mutational analysis. IGF2R gene were reported to be mutated in human tumors, resulting in tumor cell growth by inhibiting the activation of transformaing growth factor β (TGFβ) and through IGF1R pathway. We determined and registered the genomic structure of the gene into GenBank. A mutation in a adenocarcinoma of the lung was found. PTH2, a reported PTEN/MMAC1 homologue, was analyzed and seemed to be a pseudogene. In PTEN/MMAC1 mutation analysis, allelic losses were found in 33.3% of primary lung cancer with distant metastasis. In the analysis of the gene involved in mitotic checkpoint, a somatic mutation of the hBUB1 gene was found . We also determined the genomic structure of the hMAD2 gene. We will perform the mutation analysis of the hMAD2 gene and the structural and mutational analysis of other mitotic checkpoint genes.

我们对肿瘤抑制剂，胰岛素样生长因子2受体（IGF2R），PTEN/MMAC1，其同源性，HBUB1和HMAD2基因进行了结构分析。我们还进行了他们的突变分析。据报道，IGF2R基因在人类肿瘤中被突变，通过抑制转化生长因子β（TGFβ）和通过IGF1R途径的激活而导致肿瘤细胞的生长。我们确定并将基因的基因组结构注册到GenBank中。发现了肺Deocarcinoma中的突变。 PTH2是据报道的PTEN/MMAC1同源物，已分析，似乎是假基因。在PTEN/MMAC1突变分析中，在有不同转移的原发性肺癌中发现了等位基因损失。在对涉及有丝分裂检查点的基因的分析中，发现了HBUB1基因的体细胞突变。我们还确定了HMAD2基因的基因组结构。我们将对HMAD2基因的突变分析以及其他有丝分裂检查点基因的结构和突变分析。

项目成果

Akihiko Gemma: "Mutation analysis of the gene encoding the human mannose 6 phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) in cell lines resistant to growth inhibition by transforming growth factor β1 (TGFβ1)."Lung Cancer. (in press).

Akihiko Gemma：“对转化生长因子 β1 (TGFβ1) 抑制生长的细胞系中编码人甘露糖 6 磷酸盐/胰岛素样生长因子 2 受体 (M6P/IGF2R) 的基因进行突变分析。”《肺癌》。按）。

Hosoya Y.: "Alteration of the PTEN/MMAC1 gene locus in primary lung cancer with distant metastasis."Lung Cancer. 25. 87-93 (1999)

Hosoya Y.：“伴有远处转移的原发性肺癌中 PTEN/MMAC1 基因位点的改变。”肺癌。

Gemma A.: "Mutation analysis of the gene encoding the human mannose 6 phosphate/insulin-like growth factor 2 receptor(M6p/IGF2R) in human cell lines resistant to growth inhibition by transforming growth factor β1(TGFβ1)"Lung Cancer. (in press). (2000)

Gemma A.：“对转化生长因子 β1 (TGFβ1) 抑制生长的人类细胞系中编码人甘露糖 6 磷酸盐/胰岛素样生长因子 2 受体 (M6p/IGF2R) 的基因进行突变分析”肺癌。 2000)

Gemma A.: "Mutation analysis of the gene encoding the human mannose 6 phosphate/insulin-like growth factor 2 receptor (M6P/1GF2R) in human cell lines resistant to growth inhibition by transforming growth factor β1(TGFβ1)"Lung Cancer. (in press). (2000)

Gemma A.：“对转化生长因子 β1 (TGFβ1) 抑制生长的人类细胞系中编码人甘露糖 6 磷酸盐/胰岛素样生长因子 2 受体 (M6P/1GF2R) 的基因进行突变分析”肺癌。 (2000)

Yoko Hosoya: "Alteration of the PTEN/MMAC1 gene locus in primary lung cancer with distant metastasis."Lung Cancer. 25. 87-93 (1999)

Yoko Hosoya：“原发性肺癌远处转移中 PTEN/MMAC1 基因位点的改变。”肺癌。