NEW NUCLEAR MATRIX PROTEIN IN BREAST CANCER GROWTH

描述(申请人的描述)： 这位候选人的研究经验是在乳腺癌领域。 在她的博士后工作中，她能够证明热休克蛋白 (特别是Hsp27)在生长和耐药性中起着重要作用。 因此，她决定研究Hsp27的转录调控， 最终目标是确定一个可以用来操纵的因素 HSP27在乳腺癌细胞中的表达。在这些研究中，她克隆了一个 一种与最近克隆的一种新蛋白(HET)明显相同的新蛋白 支架附着因子/核基质蛋白。在过去的一年里 候选人开始分析HET，发现HET确实是一个核 基质蛋白，它可以与基质附着区(MAR)结合，以及 它扮演着转录抑制因子的角色。此外，HET还拥有许多 肿瘤抑制物样特性，包括对肿瘤的抑制 其染色体基因座的生长和杂合性丧失。她的结果 很快明确表示，尽管HET最初被确认为HSP27 启动子结合蛋白有许多更重要的功能， 这需要进一步的调查。建议的研究是基于 这些发现，它们现在定义了候选人感兴趣的领域 这与她的同事是分开的，但允许她从 她在博士后分部的博士后工作中获得的专业知识 医学肿瘤学。应聘者将在以下期间接受额外培训 第一年和第二年来自赞助商肯特·奥斯本博士，他是 转译乳腺癌研究。到公元03年，候选人将成为 完全独立的调查员。拟议研究的目标是 描述HET对乳腺癌生长的影响，并确定可能的 机制(例如，确定可能涉及的HET靶基因 在细胞周期调节中)。这项研究将为基础研究提供新的见解 乳腺癌生长的机制，并可能最终导致新的治疗方法 通过靶向在肿瘤生长中起关键作用的核基质蛋白。

DESCRIPTION (Applicant's Description): The candidate's research experience is in the field of breast cancer. During her postdoctoral work she was able to show that heat shock proteins (specifically hsp27) play an important role in growth and drug resistance. She therefore decided to study the transcriptional regulation of hsp27, with the final goal of identifying a factor which could be used to manipulate hsp27 levels in breast cancer cells. During these studies she cloned a novel protein (HET) which apparently is identical to a recently cloned scaffold attachment factor/nuclear matrix protein. During the last year the candidate started analyzing HET and found that HET indeed is a nuclear matrix protein, that it can bind to matrix attachment regions (MAR), and that it acts as a transcriptional repressor. Furthermore, HET has many tumor suppressor-like c h a r a cteristics, including inhibition of tumor growth and loss of heterozygosity at its chromosomal locus. Her results soon made it clear that although HET was originally identified as an hsp27 promoter binding protein, i t m a y have many more important functions, which warrant further investigation. The proposed studies are based upon these findings, and they now define an area of interest for the candidate which is separate from that of her colleagues, but allows her to draw from the expertise she has gained during her postdoctoral work in the Division of Medical Oncology. The candidate would obtain additional training during years 1 and 2 from sponsor Dr. Kent Osborne, who is an expert in translational breast cancer research. By Year 03, the candidate will be a fully independent investigator. The goal of the proposed studies is to characterize HET's effect on breast cancer growth, and identify possible mechanisms (e.g. identification of HET target genes which might be involved in cell cycle regulation). This study will provide new insight into basic mechanisms of breast cancer growth, and may ultimately lead to new therapies by targeting a nuclear matrix protein critical in tumor growth.