TELOMERASE ASSOCIATED FACTORS AND THEIR ROLES IN CANCER PROGRESSION

端粒酶相关因子及其在癌症进展中的作用

• 批准号: 7724195
• 负责人: ELIZABETH H BLACKBURN
• 金额: $ 0.81万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7724195
• 关键词: Affinity Chromatography; Biochemistry; Cancer Cell Growth; Cancer cell line; Cell Proliferation; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA Microarray Chip; DNA Microarray format; Data; Disruption; Double-Stranded RNA; Funding; Gene Expression; Grant; Growth; HeLa S3; Human; Induction of Apoptosis; Institution; Interferons; Malignant Neoplasms; Mass Spectrum Analysis; Microarray Analysis; Proteins; Protocols documentation; Research; Research Personnel; Resources; Ribonucleoproteins; Role; Small Interfering RNA; Source; Structure; Telomerase; Telomerase RNA Component; Telomerase inhibition; Telomere Length Maintenance; Telomere Shortening; United States National Institutes of Health; cancer cell; cell growth; novel; response; telomere; tumor progression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cancer cells commonly upregulate the ribonucleoprotein-telomerase. Inhibition of telomerase has previously been predicted to slow cancer growth, but only after a sufficient period elapses for telomere shortening to occur. Recently, we have inhibited cancer cell growth specifically by inhibiting telomerase function through an siRNA targeting the template region of wild-type telomerase RNA. Expression of such siRNA in cancer cells resulted in dramatic reduction of telomerase activity, rapid inhibition of cell growth and induction of apoptosis. Unexpectedly, those potent cellular effects were not apparently induced by the disruption of telomere structures, suggesting that inhibition of telomerase by siRNA may inhibit a function of telomerase in cancer cells other than telomere length maintenance. DNA microarray analysis in these cells indicates rapid changes in growth-related gene expression that is independent of interferon response triggered by double stranded RNA. These data suggested that telomerase may be essential for cancer cell proliferation in addition to telomere length maintenance. Therefore, a main focus of our research is to further understand the underlying mechanisms by which telomerase regulates cell proliferation through identification of novel telomerase associated factors. Biochemistry purification of telomerase complexes from human cancer cell line Hela S3 has been achieved using Tandem affinity purification (TAP) protocol. Proteins associated specifically with telomerase will be isolated and identified by Mass Spectrometry.

这个子项目是众多研究子项目之一