BCL-2 FAMILY AND P53 GENES ALTER APOPTOSIS IN GLIOMAS

BCL-2 家族和 P53 基因改变胶质瘤细胞凋亡

基本信息

批准号：
6343837
负责人：
KEITH M RICH
金额：
$ 22.6万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-01-01 至 2001-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6343837
关键词：
BCL2 gene /protein apoptosis gene induction /repression glioma human genetic material tag human tissue mutagens neoplasm /cancer genetics neoplasm /cancer pharmacology neoplastic growth p53 gene /protein protooncogene tissue /cell culture tumor suppressor genes tumor suppressor proteins

项目摘要

DESCRIPTION (Applicant's abstract): Primary malignant brain tumors respond poorly to treatment with chemotherapy or radiotherapy. The great majority of these tumors ar resistant to long-term control, and patients survive usually only a couple of years after diagnosis. Alterations in expression of p53 and bcl-2 gene family members influence cell growth and apoptotic cell death in a number of types of tumors, but their roles, either individually or together, in evaluating the biological behavior of gliomas have not been well defined. This proposal is directed towards evaluating the importance of p53 and bcl-2 gene family member function on cellular proliferation and death in gliomas following treatment with the DNA damaging agents commonly used clinically, as well with newer treatment strategies undergoing laboratory and/or clinical investigations. With use of two human glioma cell lines, U87 (which expressed wild type p53) and U373 ( which expresses only mutant p53), the hypotheses that regulation of the ratio of promotors of apoptosis (i.e. bax and its homologues) to in-hibitors of apoptosis (i.e. bcl-2 and its homologues) will determine radio-and chemo-sensitivity in gliomas will be tested. Clones will be constructed that over-express wild type p53, bax, bcl-2, or bcl-x. The effects of these transfections on chemo- and radio-sensitivity will be correlated with the changes in the ratio of promotors to inhibitors of apoptosis. This hypothesis will be tested in clinically derived tumor specimens a s well. With assistance from the Washington University Tumor Bank , Molecular diagnosis core and neuro-oncology tumor board, patient's clinical responses to treatment will be correlated with molecular changes in expression of p53 and bcl-2 gene family members measured in fresh tissue specimens obtained from the neurosurgery operating rooms. This strategy will allow for the determination of the importance of functional p53, and its interactions with members of the bcl-2 gene family in determining response to both traditional and new chemo- and radio-therapy treatments.

描述（申请人的摘要）：主要恶性脑肿瘤反应化学疗法或放射疗法的治疗不佳。绝大多数这些肿瘤对长期控制的抗药性，患者存活通常在诊断后仅几年。表达的改变 p53和Bcl-2基因家族成员影响细胞生长和凋亡多种类型的肿瘤中的细胞死亡，但它们的作用是单独或一起评估神经胶质瘤的生物学行为尚未得到很好的定义。该提案针对评估 p53和Bcl-2基因家族成员在细胞上的重要性 DNA损伤治疗后神经胶质瘤的增殖和死亡代理在临床上常用的代理以及新的治疗策略接受实验室和/或临床研究。使用两种人神经胶质瘤细胞系U87（表达野生型p53）和U373（仅表达突变体p53），假设调节凋亡启动子（即Bax及其同源物）与细胞凋亡（即Bcl-2及其同源物）的纤维内纤维将决定将测试神经胶质瘤中的无线电和化学敏感性。克隆会构建了过表达的野生型P53，BAX，BCL-2或BCL-X。这这些转染对化学敏感性和无线敏感性的影响将是与启动子与抑制剂之比的变化相关凋亡。该假设将在临床衍生的肿瘤中进行检验标本很好。在华盛顿大学肿瘤的帮助下银行，分子诊断核心和神经肿瘤肿瘤板，患者对治疗的临床反应将与分子变化相关在新鲜组织中测得的p53和Bcl-2基因家族成员的表达从神经外科手术室获得的标本。这个策略将允许确定功能p53的重要性，并确定它与Bcl-2基因家族成员的相互作用在确定对传统和新的化学治疗治疗的反应。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Tissue transglutaminase 2 inhibition promotes cell death and chemosensitivity in glioblastomas.

组织转谷氨酰胺酶 2 抑制可促进胶质母细胞瘤的细胞死亡和化疗敏感性。

DOI：
10.1158/1535-7163.mct-04-0328
发表时间：
2005
期刊：
Molecular cancer therapeutics
影响因子：
5.7
作者：
Yuan,Liya;Choi,Kihang;Khosla,Chaitan;Zheng,Xiao;Higashikubo,Ryuji;Chicoine,MichaelR;Rich,KeithM
通讯作者：
Rich,KeithM

Transfection of C6 glioma cells with the bax gene and increased sensitivity to treatment with cytosine arabinoside.

用bax基因转染C6神经胶质瘤细胞并增加对阿糖胞苷治疗的敏感性。