APC2 AND BREAST CANCER

APC2 和乳腺癌

• 批准号: 6514689
• 负责人: STEPHEN W BYERS
• 金额: $ 11.64万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-04 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6514689
• 关键词: breast neoplasms; cadherins; cyclins; estrogen receptors; fluorescent in situ hybridization; gel electrophoresis; gene expression; gene mutation; genetic markers; loss of heterozygosity; neoplasm /cancer genetics; ovary neoplasms; protooncogene; recombinant proteins; tissue /cell culture; tumor suppressor genes

DESCRIPTION: (Applicant's Description) A second member of the APC tumor suppressor family (APC2) was recently identified in this and other laboratories. Preliminary results show that APC2 associates with actin filaments and with the Golgi apparatus, and that like APC, APC2 is able to bind to and down-regulate beta-catenin, a member of the wnt signal transduction cascade. Although the wnt/APC/beta-catenin signaling pathway has been implicated in breast cancer no significant genetic changes in beta-catenin or APC occur in human breast cancers as they do in colon, ovarian and hepatocellular carcinomas. We have now fine mapped APC2 to a region of chromosome 19p13.3 that is subject to loss of heterozygosity (LOH) in several cancers including, most commonly, breast cancer. It is the goal of the present study to investigate the cytogenetics of this putative tumor suppressor gene. Specifically we will test the hypothesis that LOH and/or mutation of APC2 is associated with breast cancers with 19p loss. Targets of beta-catenin signaling include cyclin Dl and c-myc, both of which are commonly overexpressed in human breast cancers. We will relate the cytogenetics of APC2 to the expression of cyclin D1 and c-myc breast cancers.

描述：（申请人的描述） APC肿瘤抑制家族的第二个成员（APC 2）最近被发现。 在这个实验室和其他实验室里发现的。 初步结果显示，APC 2 与肌动蛋白丝和高尔基体等相连 APC，APC 2能够结合并下调β-连环蛋白，β-连环蛋白是APC的一个成员。 Wnt信号转导级联反应。 尽管wnt/APC/β-连环蛋白信号转导 通路与乳腺癌有关， β-连环蛋白或APC出现在人类乳腺癌中，就像它们在结肠癌、卵巢癌和乳腺癌中一样。 和肝细胞癌。 我们现在已经将APC 2精细映射到 染色体19 p13.3，在几个基因中存在杂合性丢失（洛）， 癌症，最常见的包括乳腺癌。 这是我们的目标。 本研究旨在探讨这种假定肿瘤的细胞遗传学 抑制基因 具体地说，我们将检验洛缺失和/或 APC 2的突变与具有19 p丢失的乳腺癌相关。 目标 β-连环蛋白信号传导包括细胞周期蛋白D1和c-myc，两者通常都是 在人类乳腺癌中过度表达。 我们将从细胞遗传学的角度 APC 2对cyclin D1和c-myc表达的影响。

项目成果

Human APC2 localization and allelic imbalance.

• 发表时间: 2001-11
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: C. Jarrett;J. Blancato;T. Cao;D. Bressette;M. Cepeda;P. Young;C. King;S. Byers