PERINUCLEOLAR COMPARTMENT AS A PUTATIVE CANCER MARKER

描述：（申请人的摘要）核仁周围区室（PNC）是一种 动态的、形状不规则的、电子致密的核结构，即 与核仁有物理联系。全国民警委员会被发现 主要在转化的培养细胞和几种检查的癌症样品中， 但在正常成纤维细胞和上皮中很少检测到。两 hnRNP和几种小RNA已被发现在PNC中富集， 申请人最近的研究表明PNC参与转录 和RNA代谢。多聚嘧啶束结合蛋白（PTB）， 与PNC相关的RNA结合蛋白，以显著更高的水平表达。 转化细胞与非转化细胞相比的水平。这些发现 提示PNC形成和PTB表达增加可能代表了 恶性转化细胞中细胞和分子活性的变化。的 申请人的目标是研究PNC形成、PTB 表达水平和体内人恶性肿瘤，并评估 使用PNC和PTB浓度作为特异性肿瘤标志物的可能性。在 在这项申请中，申请人将寻求完成两项试点实验， 以乳腺癌为模型的研究。在第一个目标中，申请人 将检查和比较PNC的患病率（包含 一个或多个PNC）在正常、良性、癌前和恶性乳腺组织中 样本，并将确定PNC患病率之间的统计相关性 以及处于不同发展阶段和恶性程度的乳腺癌。 在第二个目标中，申请人将检查和比较表达水平 PTB蛋白在相似范围的乳腺组织中的表达。通过拟议的 研究，申请人希望获得初步的见解PNC是否 患病率和PTB浓度可能有助于癌症诊断， 预后

DESCRIPTION: (Applicant's Abstract) The perinucleolar compartment (PNC) is a dynamic, irregularly shaped, and electron dense nuclear structure, that is physically associated with the nucleolus. The PNC has been found to be present predominantly in transformed culture cells and several cancer samples examined, but it has been rarely detected in normal fibroblasts and epithelium. Two hnRNPs and several small RNAs have been found enriched in the PNC and the applicant's recent studies suggest that the PNC is involved in transcription and RNA metabolism. The polypyrimidine tract binding protein (PTB), one of the PNC-associated RNA binding proteins, is expressed at a significantly higher level in transformed cells compared to non-transformed cells. The findings suggest that formation of the PNC and increased PTB expression may represent changes of cell and molecular activities in malignantly transformed cells. The applicant's goal is to examine the relationship between PNC formation, PTB expression levels, and human malignancy in vivo, and to evaluate the possibility of using PNCs and PTB concentration as specific tumor markers. In this application, the applicant will seek to accomplish two pilot experimental studies using breast cancer as a model system. In the first aim, the applicant will examine and compare PNC prevalence (the percentage of cells that contain one or more PNCs) in normal, benign, premalignant, and malignant breast tissue samples, and will determine the statistical correlation between PNC prevalence and breast cancers at various stages of progression and degrees of malignancy. In the second aim, the applicant will examine and compare the expression level of the PTB protein in a similar range of breast tissues. Through the proposed studies, the applicant hopes to gain preliminary insights into whether PNC prevalence and PTB concentration could be useful in cancer diagnosis and prognosis.