Prostate Cancer--Mechanisms of Bax induced Cell Death

前列腺癌--Bax诱导细胞死亡的机制

• 批准号: 6522658
• 负责人: JIALING XIANG
• 金额: $ 9.92万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6522658
• 关键词: Bax gene /protein; androgens; apoptosis; athymic mouse; cell growth regulation; cysteine endopeptidases; enzyme activity; enzyme induction /repression; hormone regulation /control mechanism; hormone related neoplasm /cancer; male; neoplasm /cancer chemotherapy; neoplasm /cancer genetics; nonhuman therapy evaluation; paclitaxel; prostate neoplasms

the development of androgen-independence by prostate cancer cells is a major hurdle in the treatment of prostate cancer with conventional therapies. The major molecular defect is that the cancer cells fail to initiate programmed cell death (apoptosis) in response to various eupeptic stimuli. Recently we have found that over expression of bad, which is a pro-apoptotic molecule and a counterpart of BCL-2, includes apoptose in prostate cancer cells. In fact, androgen-independent LNCaP cells are even more sensitive to Bad-induced cell death than their androgen-dependent counterparts. Furthermore, subcellular localizations of Bad appear to be different in androgen-dependent and independent LNCaP cells. We hypothesize that Bad may play a critical role in the balance between cell survival and death in androgen-independent prostate cancers. We propose to investigate the molecular mechanisms underlying Bad-induced apoptosis in prostate cancer cells, as well as its relationship to the androgen-independent in vitro and in vivo. This work is novel as it will shed light on the interplay between an eupeptic pathway and androgen regulation and might have therapeutic implications for prostate cancer. The training environment for the applicant is excellent. Dr. Shustung Liam, the ,mentor, has been studying androgen regulation and prostate cancer for more tan 40 years and his group has made several ground breaking contributions to the field. The Ben May Institution for Cancer Research has long tradition for prostate cancer research, starting from the Noble Prize winning work of Dr. Huggins on treatment of prostate cancer. The University of Chicago has several excellent prostate cancer research programs. With many investigators and exports working in the field of prostate cancer and many Core facilities, including a prostate tissue bank. With the excellent training I have received in the fields of cycle regulation, apoptosis and gene therapy, I am confident that I will be able to pursue the proposed studies and make a successful transition into the front tier of prostate cancer research. The financial support provided by this NIH award will allow me to complete my training and to launch my carrier ad an independent investigator in an academic setting.

前列腺癌细胞独立于雄激素的发展是治疗前列腺癌的主要障碍。主要的分子缺陷是癌细胞无法响应各种成熟刺激而引发程序性细胞死亡（细胞凋亡）。最近，我们发现过度表达不良，这是一种促凋亡分子，Bcl-2的对应物包括前列腺癌细胞中的凋亡。实际上，与雄激素依赖性依赖性对应物相比，与雄激素无关的LNCAP细胞对不良诱导的细胞死亡更敏感。此外，在雄激素依赖性和独立的LNCAP细胞中，不良的亚细胞位置似乎有所不同。我们假设坏蛋可能在雄激素独立的前列腺癌中的细胞存活与死亡之间的平衡中起关键作用。我们建议研究前列腺癌细胞中不良诱导的细胞凋亡的分子机制，以及与雄激素非依赖性体外和体内的关系。这项工作是新颖的，因为它将阐明神能途径和雄激素调节之间的相互作用，并可能对前列腺癌具有治疗意义。申请人的培训环境非常好。导师Shustung Liam博士一直在研究雄激素调节和前列腺癌已有40年了，他的小组为该领域做出了几项破坏性的贡献。 Ben May癌症研究机构具有长期的前列腺癌研究的传统，从Huggins博士在治疗前列腺癌治疗的贵族奖项开始。芝加哥大学有几个出色的前列腺癌研究计划。许多研究人员和出口在前列腺癌和许多核心设施中工作，包括前列腺组织库。在我在周期调节，凋亡和基因治疗领域接受过的出色培训，我相信我将能够进行拟议的研究，并成功地过渡到前列腺癌研究的前层。 NIH奖提供的财政支持将使我能够完成培训，并在学术环境中推出一名独立调查员。