Genetic alterations involved in initiation and progression of human pancreatic cancer

基因改变参与人类胰腺癌的发生和进展

• 批准号: 09470049
• 负责人: HORII Akira
• 金额: $ 8万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470049/
• 关键词: tumor suppressor gene; pancreatic cancer; 6q; 12q; 17p; 18q; the DUSP6 gene; the TDG gene; SMAD4遺伝子; FISH; DNAミスマッチ修復異常招; 染色体6番長腕; 染色体12番長腕; 染色体20番長腕; IGFIIレセプター; BAX

1.We previously identified frequently deleted region in human pancreatic cancer in chromosome arms 1p, 6q, 9p, 12q, 17p, and 18q. Among these regions, losses of 12q, 17p, and 18q were found to associated with poor prognosis in human pancreatic cancer. 17p and 18q are the loci for TP53 and SMAD4, respectively.2.On 6q and 12q, three and two smallest regions of overlap (SROs), respectively, were identified. BAC contigs for one region on 6q and two regions on 12q were constructed, and some genes in these regions were analyzed.3.DUSP6 on 12q21 and TDG on 12q24 were analyzed. Although no genomic alterations were found, loss or suppressed expression in pancreatic cancer cell lines were observed, suggesting the involvement of suppressed expression of these genes in human pancreatic carcinogenesis.4.Adenoviral mediated delivery of the SMAD4 gene in pancreatic cancer cell lines with homozygous deletion of SMAD4 did not show any suppression of cell growth. We think that inactivation of the SMAD4 gene is not associated with acceleration of cell growth but associated with some other mechanisms in pancreatic carcinogenesis.5.We reported that loss of 18q is an early event in pancreatic carcinogenesis. There is a possibility that mutation of the SMAD4 gene is responsible for the initial step of pancreatic carcinogenesis as well as prognosis defining factor. However, there is a possibility of unknown tumor suppressor gene on 18q that is distinct from SMAD4.

1.我们先前在人类胰腺癌中经常识别出染色体臂1p，6q，9p，12q，12q，17p和18q的区域。在这些区域中，发现12q，17p和18q的损失与人类胰腺癌的预后不良有关。 17p和18q分别是TP53和SMAD4的基因座。2.N6Q和12Q，分别确定了重叠的三个和两个最小的区域（SRO）。构建了一个区域的一个区域的BAC重叠群，并在12q上构建了两个区域，并分析了这些区域的某些基因。3.DUSP6在12q21和12q24上的TDG上进行了分析。尽管未发现基因组改变，但观察到胰腺癌细胞系中的丧失或抑制表达，这表明这些基因在人胰腺癌发生中抑制了这些基因的表达。 Smad4的含量没有显示出对细胞生长的任何抑制。我们认为，SMAD4基因的失活与细胞生长的加速无关，而与胰腺癌中的其他一些机制有关。5.5。我们报道，18q的丧失是胰腺癌发生的早期事件。 Smad4基因的突变可能是胰腺癌发生的第一步以及预后定义因子的第一步。但是，在18Q上可能会在18Q上抑制未知的肿瘤基因，这与SMAD4不同。

项目成果

Cloning and characterization of the human UDP-N-acetylglucosamine:a-1,3-D-mannosideb-1,4-N-acetylglucosaminyltransferase IV-homologue (hGnT-IV-H) gene.

人 UDP-N-乙酰氨基葡萄糖：a-1,3-D-甘露糖苷b-1,4-N-乙酰氨基葡萄糖转移酶 IV 同源物 (hGnT-IV-H) 基因的克隆和表征。

• 发表时间: 1999
• 期刊: J.Hum.Genet. 44
• 作者: Furukawa;T.;Youssef;E.M.;Yatsuoka;T.;Yokoyama;T.;Makino;N.;Inoue;H.;Fukushige;S.;Hoshi;M.;Hayashi;Y.;Sunamura;M.;Horii;A.
• 通讯作者: A.

The BAX gene, the promoter of apoptosis, is mutated in genetically unstable cancers of the colorectum, stomach, and endometrium.

• 发表时间: 1998-04
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: H. Ouyang;T. Furukawa;T. Abe;Y. Kato;A. Horii

Yatsuoka,T.: "Genomic analysis of the thymine-DNA glycosylase(TDG)gene on 12q22-q24.1 in human pancreatic ductal adenocarcinoma." International Journal of Pancreatology. (in press).

Yatsuoka,T.：“对人胰腺导管腺癌 12q22-q24.1 上的胸腺嘧啶 DNA 糖基化酶 (TDG) 基因进行基因组分析。”

Abe,T.: "Identification of three commonly deleted regions on chromosome arm 6q in human pancreatic cancer." Genes,Chromosomes & Cancer. (in press).

Abe,T.：“人类胰腺癌染色体臂 6q 上三个常见缺失区域的鉴定。”

Fukushige,S.: "Loss of chromosome 18q is an early event in pancreatic duc-tal tumorigenesis." Cancer Research. 58. 4222-4226 (1998)

Fukushige,S.：“18q 染色体丢失是胰腺导管肿瘤发生的早期事件。”