Analysis of the genetic and molecular pathogenesis in enteropancreatic neuroendocrine tumors

肠胰神经内分泌肿瘤的遗传和分子发病机制分析

基本信息

批准号：
14370354
负责人：
KOMOTO Izumi
金额：
$ 6.02万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

Enteropancreatic neuroendocrine tumors constitute a wide variety of rare lesions that are named according to the hormones that they produce. Although these tumors generally are believed to have an indolent growth pattern, the subset of tumors have an aggressive course. Unfortunately, in an individual patient there are no clinical, laboratory, or tumor histological features that reliably predict which the tumor will pursue an aggressive course. Furthermore, the molecular mechanisms responsible for the development and/or progression of Enteropancreatic neuroendocrine tumors are largely unknown.We previously demonstrated that human normal islet cells and insulinoma cells express the calcium-sensing receptor (CaR), and that the response of normal islets and insulinoma cells to change in extracellular Ca concentration was different. To investigate the genetic and molecular pathogenesis of the enteropancreatic neuroendocrine tumors, we analyzed the expression patterns of these tumors. We' ob … More tained the analysis of the data from tumor samples and extracted the some candidate genes involved in nodal metastasis of tumors. Here, we focused on the cell differentiation molecules, including NOTCH2 and PDX1 from the candidate genes. The expression patterns of PDX1, somatostatin, and serotonin were associated with the primary location of the tumors and with the tumors occurring in a sporadic fashion or a hereditary fashion. PDX1 was expressed in a115 duodenal gastrinomas, whereas its expression was reduced in 4 pancreatic tumors. Furthermore, the PDX1 was absent in the tumor occurring in a sporadic fashion, and was expressed in all tumors with MEN1. The difference in expression pattern of these genes was possibly, caused by the different origin of the tumors. Further investigation of the cell differentiated genes could result in the identification of the target genes and prognostic factors in the enteropancreatic neuroendocrine tumor. If molecular prognostic factors could be identified that accurately predicted the growth behavior of tumors in an individual patient, more aggressive treatment could be started earlier in the subset with a poor prognosis. Less

肠胰腺神经内分泌肿瘤由多种罕见病变组成，根据它们产生的激素命名，尽管这些肿瘤通常被认为具有惰性生长模式，但不幸的是，在个别患者中，肿瘤的亚型具有侵袭性病程。没有临床、实验室或肿瘤组织学特征可以可靠地预测肿瘤将进行侵袭性过程。此外，导致肠胰腺神经内分泌肿瘤发生和/或进展的分子机制在很大程度上是未知的。我们之前证明了。人类正常胰岛细胞和胰岛素瘤细胞表达钙敏感受体（CaR），并且正常胰岛细胞和胰岛素瘤细胞对细胞外Ca浓度变化的反应不同。我们分析了这些肿瘤的表达模式。我们对肿瘤样本的数据进行了分析，并提取了一些与肿瘤淋巴结转移相关的候选基因，包括细胞分化分子。候选基因中的NOTCH2和PDX1的表达模式与肿瘤的原发位置以及以散发性或遗传性方式发生的肿瘤有关，而PDX1在a115十二指肠胃泌素瘤中表达。它的表达在 4 个胰腺肿瘤中降低，此外，PDX1 在零星发生的肿瘤中不存在，并且在所有胰腺肿瘤中表达。 MEN1。这些基因的表达模式差异可能是由肿瘤的不同起源引起的，进一步研究细胞分化基因可以确定肠胰腺神经内分泌肿瘤的靶基因和预后因素。如果可以确定能够准确预测个体患者肿瘤生长行为的因素，则可以在预后较差的亚组中更早开始更积极的治疗。