Role of SENP1 in Prostate Cancer Pathogenesis

SENP1 在前列腺癌发病机制中的作用

基本信息

批准号：
7295961
负责人：
Tasneem Bawa-Khalfe
金额：
$ 1.45万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2007-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7295961
关键词：
Ablation Adenocarcinoma Agar Age Anchorage-Independent Growth Androgen Receptor Androgens Apoptosis Attenuated Biological Cancer Cell Growth Cancer Etiology Carcinoma Cell Count Cell Cycle Progression Cell Proliferation Cells Cessation of life Cleaved cell Data Development Diagnosis Disease Dose Doxycycline Dysplasia Elevation Endopeptidases Epithelium Fellowship Genetic Transcription Growth HDAC1 gene Hormones Human In Situ Hybridization In Vitro Individual LNCaP Laboratories Lesion Lobe Malignant Neoplasms Malignant neoplasm of prostate Mediating Modification Mus Names Neoplasm Metastasis Nude Mice Onset of illness Pathogenesis Pathway interactions Peptide Hydrolases Proliferating Property Prostate Protein Overexpression Proteins Receptor Activation Reporting Role Soft Agar Assay Specimen Stimulation of Cell Proliferation System Testing Tetracycline Tetracyclines Tissues Transgenic Mice Transgenic Organisms Ubiquitin Ubiquitin Like Proteins Up-Regulation Wild Type Mouse Xenograft procedure Yeasts cancer cell cancer diagnosis carcinogenesis cell growth cell transformation enzyme activity in vivo isopeptidase male men probasin promoter tumor tumor growth tumor progression tumorigenic

项目摘要

DESCRIPTION (provided by applicant): Our laboratory cloned the first human sentrin/SUMO-specific protease, SENP1. The isopeptidase activity of this enzyme deconjugates the posttranslation modification by SUMO (small ubiquitin-like modifier). Although its catalytic activity has been characterized, the biological significance of SENP1 remains unknown. Recently we observed that SENP1 enhances androgen receptor (AR)-dependent transcription. Numerous reports conclude that enhancement of AR activity promotes development of prostate cancer (PCa), the most frequently diagnosed carcinoma in males. In situ hybridization studies indicate an overexpression of SENP1 in pre-cancer and cancer lesions, but not normal prostate epithelia. Also, stable overexpression of SENP1 prompts PCa cell growth and transformation. Currently, it is unknown whether enhanced expression of SENP1 promotes prostate carcinogenesis; hence we propose to test whether induction of SENP1 regulates the development and progression of prostate cancer. Using an inducible system, the effect of SENP1 expression on proliferation of LNCaP cells and tumor growth in nude mice will be explored. Also, transgenic mice overexpressing SENP1 in the prostate will be evaluated for tumor formation and aggressiveness.

描述（由申请人提供）：我们的实验室克隆了第一个人类哨兵/SUMO特异性蛋白酶，SENP1。该酶的异肽酶活性通过Sumo（小泛素样修饰剂）进行了反翻译后修饰。尽管其催化活性已被表征，但SENP1的生物学意义仍然未知。最近，我们观察到SENP1增强了雄激素受体（AR）依赖性转录。许多报道得出的结论是，AR活性的增强促进了前列腺癌（PCA）的发展，前列腺癌（PCA）是男性最常见的癌。原位杂交研究表明，在癌症和癌症病变中SENP1的过表达，但不是正常的前列腺上皮。此外，SENP1的稳定过表达促使PCA细胞的生长和转化。目前，尚不清楚SENP1的增强表达是否促进了前列腺癌发生。因此，我们建议测试SENP1的诱导是否调节前列腺癌的发展和进展。使用诱导系统，将探索SENP1表达对LNCAP细胞增殖和裸鼠肿瘤生长的影响。此外，将评估前列腺中过表达SENP1的转基因小鼠的肿瘤形成和侵略性。