THE JAZF1 AND 2 GENES IN UTERINE SARCOMAS

子宫肉瘤中的 JAZF1 和 2 基因

• 批准号: 6522595
• 负责人: Jeffrey Sklar
• 金额: $ 30.29万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-08 至 2004-01-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6522595
• 关键词: antisense nucleic acid; athymic mouse; chromosome translocation; complementary DNA; female; fusion gene; gene mutation; genetically modified animals; human tissue; microarray technology; neoplasm /cancer genetics; nucleic acid sequence; oligonucleotides; protein structure function; sarcoma; transcription factor; uterus neoplasms; women's health; yeast two hybrid system

DESCRIPTION: (Adapted from the investigator's abstract) Dr. Sklar has identified two previously unknown genes, termed JAZF1 and 2, which are fused in low grade endometrial stromal sarcomas (ESSs) as a consequence of a recurrent (7;17)(p15;q21) chromosomal translocation associated with these tumors. Both genes encode proteins containing zinc finger domains, and in JAZF1, the sequences of codons for two such domains closely resemble the sequence for two zinc fingers found in the transcription factor Sfplp, which has recently been implicated in the mechanism governing the G2/M checkpoint in the cell cycle of S. cervesiae. He proposes to characterize the JAZF1 and 2 genes in tumors and normal tissues through a series of studies, beginning with the completion of nucleotide sequence analysis of the amino terminal ends of the normal coding sequences, which have not yet been located. A wide variety of uterine and non-uterine sarcomas will be screened for the fusion transcript and mutations of the JAZF1 gene to determine the range of neoplasms containing abnormalities in the two genes and to answer a number of outstanding questions regarding the classification and histogenesis of uterine stromal tumors. Additionally, the ability of the JAZF1/JAZF2 fusion to induce malignant transformation will be investigated using both cultured cells and transgenic mice. Gene expression altered by the presence of the JAZF1/JAZF2 fusion will be analyzed by examining transcription profiles in cultured cells carry cDNA for the two genes transfected into bacteria. Interactions between the protein products of the two genes and other proteins will be explored using the yeast two-hybrid system. Phenotypic effects of the murine homologs for the JAZF1 and 2 will be assessed in knockout animals separately defective in both alleles. Finally, DNA binding sites for the two proteins will be sought and the sequences of these sites will be used in turn to identify genes transcriptionally regulated by JAZF1 and 2 in normal cells.

描述：（改编自研究者摘要）Sklar博士 发现了两个以前未知的基因，称为JAZF 1和2，它们融合在 低级别子宫内膜间质肉瘤（ESS）是复发性 （7;17）（p15;q21）与这些肿瘤相关的染色体易位。两 基因编码含有锌指结构域的蛋白质，在JAZF 1中， 两个这样的结构域的密码子序列非常类似于两个这样的结构域的序列。 在转录因子Sfplp中发现的锌指， 在细胞周期的G2/M检查点的调控机制中， S. cervesiae。他建议描述肿瘤中JAZF 1和2基因的特征， 正常组织通过一系列的研究，从完成 正常编码区氨基末端的核苷酸序列分析 序列，尚未被定位。各种各样的子宫和 将对非子宫肉瘤进行融合转录本和突变筛查 JAZF 1基因，以确定包含异常的肿瘤的范围 在这两个基因，并回答了一些悬而未决的问题， 子宫间质瘤的分类和组织发生。另夕h JAZF 1/JAZF 2融合体诱导恶性转化的能力将是 使用培养细胞和转基因小鼠进行研究。基因表达 将通过检查由JAZF 1/JAZF 2融合体的存在改变的细胞的表达， 培养细胞中的转录谱携带这两个基因的cDNA 转染到细菌中。两者的蛋白质产物之间的相互作用 基因和其他蛋白质将使用酵母双杂交系统进行探索。 将评估JAZF 1和2的鼠同源物的表型效应 基因敲除动物的两个等位基因都有缺陷。最后，DNA结合 将寻找这两种蛋白质的位点，这些位点的序列将 反过来用于识别由JAZF 1和2转录调控的基因， 正常细胞