POLYMERASE CHAIN REACTIONASSAY FOR DELTA LF IN CANCER

癌症中 Delta LF 的聚合酶链反应测定

• 批准号: 2536519
• 负责人: PAUL D SIEBERT
• 金额: $ 10万
• 依托单位: CLONTECH LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2536519
• 关键词: breast neoplasms; cell line; estrogen receptors; genetic markers; histopathology; human tissue; lactoferrin; messenger RNA; method development; neoplasm /cancer genetics; polymerase chain reaction; southern blotting

Lactoferrin, which is an iron binding protein present in milk and various secretions, has emerged as a multifunctionai protein involved in the host defense against infection and tumorogenesis. We have recently identified an alternative form of LF mRNA we term ALF. Although, we find ALF mRNA in 100% (30 of 30) normal human tissues, we find ALF mRNA in only 10% (3 of 28) diverse tumor-derived cell lines. In a preliminary study, we found lower levels of ALF mRNA in 90% (9 of 10) primary breast tumor specimens compared to normal human breast tissues. In Phase I, we plan to develop a quantitative RT-PCR assay for both LF and LF mRNA. We will then quantitatively examine levels of ALF and LF mRNA in 142 fully characterized, archived breast tumor specimens collected at Stanford University Hospital. We will then correlate our results to various clinical parameters including tumor grade, histology, presence or absence of estrogen receptors, and patient age. Care will be taken to ensure anonymity of tumor specimens. Measurement of ALF or LF mRNA may be useful as a molecular marker in breast cancer and may be beneficial choosing more aggressive surgical procedures, treatment options, or in determining prognosis. PROPOSED COMMERCIAL APPLICATION: If the proposed Phase I and Phase II study is successful, and ALF is established as a general Class II tumor-suppressor gene, a quantitative assay to measure ALF mRNA will be widely useful in basic research as a kit. Further, if ALF is an useful molecular marker for breast cancer, we would license the assay to the diagnostic community.

乳铁蛋白，其是存在于牛奶中的铁结合蛋白， 作为一种多功能蛋白质参与了宿主的免疫调节， 防御感染和肿瘤发生。我们最近发现 LF mRNA的另一种形式我们称之为ALF。虽然，我们发现ALF mRNA在 在100%（30/30）正常人组织中，我们发现ALF mRNA仅在10%（3/30）正常人组织中表达。 28)不同的肿瘤衍生细胞系。在初步研究中，我们发现 90%（9/10）的原发性乳腺肿瘤标本中ALF mRNA水平较低 与正常的人类乳房组织相比。在第一阶段，我们计划发展一个 LF和LF mRNA的定量RT-PCR测定。 然后我们将 定量检测142例正常人肝组织中ALF和LF mRNA水平， 在斯坦福大学收集的特征性存档乳腺肿瘤标本 大学医院。 然后，我们将把我们的结果与各种 临床参数，包括肿瘤分级、组织学、是否存在 雌激素受体和患者年龄将注意确保 肿瘤标本的匿名性ALF或LF mRNA的测量可能是有用的 作为乳腺癌的分子标志物， 积极的外科手术，治疗方案，或在确定 预后 拟定商业应用： 如果拟议的I期和II期研究成功，并且ALF 作为一般的II类肿瘤抑制基因， 测定ALF mRNA的方法将作为一种新的方法广泛用于基础研究， 试剂盒此外，如果ALF是乳腺癌的一个有用的分子标志物，我们 将把检测许可给诊断界