UPREGULATION OF CKI P21 BY ANDROGEN IN PROSTATE CANCER

前列腺癌中雄激素对 CKI P21 的上调

• 批准号: 2767501
• 负责人: SHAN LU
• 金额: $ 3.84万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2767501
• 关键词: androgens; apoptosis; biomarker; carcinogenesis; cell growth regulation; disease /disorder model; gene expression; genetic promoter element; genetic regulation; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; male; model design /development; neoplastic cell; neoplastic process; northern blottings; oncoprotein p21; prostate neoplasms; tissue /cell culture

DESCRIPTION The prostate cancer is the second leading cause of cancer death in men. At early stage, the growth of prostate cancer is androgen-dependent and castration has been a very effective method in treating prostate cancer. Development of androgen-independent growth of prostate cancer after approximately 18 months of hormone ablation therapy is a major clinical dilemma. Goal of this study is to investigate the molecular mechanisms of CKI p21/Cip1/Waf1 in androgen-dependent and -independent growth of prostate carcinoma cells. This study is based on our observations that p21/Cip1/Waf1 gene was up-regulated by androgen and an increased basal expression of the gene was found in an androgen-independent prostate cancer cell line. This proposal will investigate the anti-apoptosis function of p21/Cip1/Waf1 gene in prostate carcinoma cells, which may confer the homeostasis of the cells in androgen-dependent manner and development of androgen-independent growth of pro-static cancer cell by increased basal expression of the gene. The molecular mechanism of androgen action on p21/Cip1/Waf1 gene expression will be elucidated. In addition, an in vivo androgen-independent prostate cancer model will be established for future therapeutic studies. Finally, the expression of the p21/Cip1/Waf1 gene in androgen-dependent and -independent prostate cancer specimens will be evaluated. If indeed an increased basal level of p21/Cip1/Waf1 gene in androgen-independent prostate cancer specimens was observed, it can be served as a clinical marker for developing androgen-dependent growth of prostate cancer.

描述 前列腺癌是男性癌症死亡的第二大原因。 在早期阶段，前列腺癌的生长是雄激素依赖性的， 阉割是治疗前列腺癌的一种非常有效的方法。 前列腺癌雄激素非依赖性生长的发展 大约18个月的激素消融治疗是一个主要的临床 困境本研究的目的是探讨其分子机制 CKI p21/Cip 1/Waf 1在雄激素依赖性和非依赖性生长中的作用 前列腺癌细胞这项研究是基于我们的观察， p21/Cip 1/Waf 1基因在雄激素的作用下表达上调， 在雄激素非依赖性前列腺中发现了该基因的表达。 癌细胞系本提案将研究抗凋亡 p21/Cip 1/Waf 1基因在前列腺癌细胞中的功能， 以雄激素依赖性方式赋予细胞稳态， 前列腺癌细胞雄激素非依赖性生长的发展 该基因的基础表达增加。的分子机制 将阐明雄激素对p21/Cip 1/Waf 1基因表达的作用。在 此外，还将建立体内雄激素非依赖性前列腺癌模型。 为未来的治疗研究奠定了基础。最后，表达 p21/Cip 1/Waf 1基因在雄激素依赖性和非依赖性前列腺中表达 将评估癌症样本。如果基础水平确实增加了 p21/Cip 1/Waf 1基因在雄激素非依赖性前列腺癌中的表达 观察到，它可以作为发展的临床标志物 雄激素依赖性前列腺癌的生长。

项目成果

Androgen induction of cyclin-dependent kinase inhibitor p21 gene: role of androgen receptor and transcription factor Sp1 complex.

• DOI: 10.1210/mend.14.5.0461
• 发表时间: 2000-05
• 期刊: Molecular endocrinology
• 作者: S. Lu;Guido Jenster;Daniel E. Epner