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ALTERATIONS IN THE PITSLRE PROTEIN KINASE IN MELANOMA

黑色素瘤中 PITSLRE 蛋白激酶的变化

基本信息

批准号：
6173161
负责人：
Mark Anthony Nelson
金额：
$ 10.69万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-05-01 至 2001-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6173161
关键词：
apoptosis cell growth regulation chromosome aberrations clone cells cytogenetics gene deletion mutation gene expression genetic mapping melanoma neoplasm /cancer genetics neoplastic growth protein kinase

项目摘要

DESCRIPTION: (adapted from the investigator's abstract) The cytogenetic studies in melanoma of this application, indicate that alterations of chromosome 1 are one of the most frequent anomalies of melanoma and that chromosome breaks frequently cluster at band region 1p36. The PITSLRE gene locus maps to band region 1p36 and appears to be involved in apoptotic signaling. Initial studies in their laboratory indicate alterations in PITSLRE gene copies and abnormal PITSLRE protein expression in melanoma. It was hypothesized that alterations in the PITSLRE gene locus on chromosome and 1p36 are involved in melanoma pathogenesis, possibly by disrupting apoptotic signaling pathways and preventing the elimination of tumor cells through normal checkpoint control. To test this hypothesis they proposed the following specific aims: 1) to determine if the PITSLRE genes are deleted in melanoma cell- lines with chromosome 1p alterations; 2) to analyze PITSLRE expression in melanoma cell lines and primary melanoma; 3) to determine the frequency of PITSLRE gene alterations in primary melanoma specimens; and 4) to determine whether PITSLRE genes play a function role in suppressing growth and/or tumorigenicity of melanoma cell lines.

描述：（改编自研究者的摘要）细胞遗传学本申请的黑色素瘤研究表明， 1 号染色体是黑色素瘤最常见的异常之一，染色体断裂频繁聚集在带区 1p36。皮特勒基因位点映射到条带区域 1p36 并且似乎参与凋亡信号传导。他们实验室的初步研究表明 PITSLRE 基因拷贝的改变和异常的 PITSLRE 蛋白黑色素瘤中的表达。据推测，改变染色体上的PITSLRE基因位点和1p36与黑色素瘤有关发病机制，可能是通过破坏细胞凋亡信号通路和通过正常检查点阻止肿瘤细胞的消除控制。为了检验这一假设，他们提出了以下具体方案目的： 1) 确定 PITSLRE 基因是否在黑色素瘤细胞中被删除 - 具有染色体 1p 改变的品系； 2) 分析PITSLRE表达在黑色素瘤细胞系和原发性黑色素瘤中； 3）确定原发性黑色素瘤标本中 PITSLRE 基因改变的频率；和 4) 确定PITSLRE基因是否发挥功能作用抑制黑色素瘤细胞系的生长和/或致瘤性。