The Role of p73 in Upper Gastrointestinal Carcinomas

p73 在上消化道癌中的作用

• 批准号: 7622547
• 负责人: ALEXANDER I. ZAIKA
• 金额: $ 26.49万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-28 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7622547
• 关键词: Adenocarcinoma; Age; Alleles; Antibodies; Apoptosis; Biological Process; Bladder; Breast; Cancer Etiology; Cell Culture Techniques; Cell Line; Cell Proliferation; Cells; Cellular biology; Clinical; Colon Carcinoma; Data; Databases; Development; ERBB2 gene; Epigenetic Process; Esophageal; Esophageal Adenocarcinoma; Esophageal carcinoma; Esophagus; Family member; Gastric Adenocarcinoma; Gastrointestinal Neoplasms; Gene Expression; Gene Expression Regulation; Gene Targeting; Genes; Human; Hypermethylation; Incidence; Induction of Apoptosis; Investigation; Kidney; Large Intestine Carcinoma; Liver; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Membrane; Messenger RNA; Modeling; Molecular; Molecular Biology Techniques; Morbidity - disease rate; Mucous Membrane; Mutate; Mutation; Neuroblastoma; Oncogenes; Oncogenic; Outcome; Ovary; Pathway interactions; Patients; Pharmaceutical Preparations; Play; Primary Neoplasm; Primary carcinoma of the liver cells; Progression-Free Survivals; Property; Protein Isoforms; Protein p53; Proteins; Publications; Regulation; Repression; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Role; Serum; Signal Pathway; Signal Transduction; Site; Staging; Staining method; Stains; Stomach; Survival Rate; TP53 gene; Time; Tissue Banking; Tissue Banks; Tissue Microarray; Transactivation; Transcript; Transcriptional Activation; Tumor Tissue; United States; Up-Regulation; Visceral; Western World; base; cancer type; clinically significant; drug sensitivity; gastrointestinal; gastrointestinal carcinoma; imprint; in vivo; loss of function mutation; malignant breast neoplasm; metaplastic cell transformation; mortality; mouse model; neoplastic cell; novel; overexpression; prognostic; programs; promoter; protein expression; receptor; response; therapeutic target; transcription factor; tumor; tumor growth; tumorigenesis

DESCRIPTION (provided by applicant): Upper gastrointestinal carcinomas (UGC) are a leading cause of cancer-related morbidity and mortality worldwide. Moreover, the incidences of proximal stomach, gastroesophageal junctional and esophageal adenocarcinomas are the fastest rising of any tumors in the United States and Western World. These tumors are characterized by a poor response to the present chemotherapeutic regiments and an overall low survival rate. The mechanisms of tumorigenesis in upper gastrointestinal tumors are unclear. p73, a new p53 family member, and its isoform deltaNp73 are increasingly recognized as key players in tumorigenesis, as well as in chemotherapeutic drug sensitivity. Upregulation of these p73 isoforms correlates with poor clinicopathological outcome in several types of tumors. However, in gastrointestinal tumors the role of the p73 gene remains unknown. Our preliminary results indicate that p73 and deltaNp73 transcripts and proteins are frequently overexpressed in UGC. At same time, these proteins have strong oncogenic effects in gastrointestinal cells, as has been demonstrated in our preliminary studies. Taken altogether, these data suggest that p73 and deltaNp73 may be involved in development or progression of UGC. We propose to delineate the role of p73 isoforms in upper gastrointestinal tumorigenesis. In addition, we aim to evaluate their clinical significance. Using a number of cellular and molecular biology techniques, we will characterize the interaction of p73 isoforms with other signaling pathways and investigate the mechanisms that regulate p73 gene expression. For the expression analysis of p73 isoforms in upper gastrointestinal carcinomas, we will employ a real-time RT-PCR analysis and immunohistochemical staining of tumor tissue arrays from our gastrointestinal cancer tissue bank. This information may provide new avenues for the development of novel prognostic and therapeutic targets. Our specific aims are: Aim 1: Characterize the clinical significance of p73 isoforms in upper gastrointestinal carcinomas. Aim 2: Characterize the biological functions of p73 isoforms in upper gastrointestinal adenocarcinomas. Aim 3: Investigate the regulation of p73 gene expression in upper gastrointestinal carcinomas.

描述（由申请人提供）：上胃肠道癌（UGC）是全球癌症相关发病率和死亡率的主要原因。此外，近端胃、胃食管交界处和食管腺癌的发病率在美国和西方世界是所有肿瘤中上升最快的。这些肿瘤的特点是对目前的化疗方案反应差，总体生存率低。上消化道肿瘤的发生机制尚不清楚。