权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Inductible mouse models for oral cancer

口腔癌诱导小鼠模型

基本信息

批准号：
7335597
负责人：
CARLOS CAULIN
金额：
$ 35.02万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-01-13 至 2009-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7335597
关键词：
Address Adult Alleles Antineoplastic Agents Area Breast Cancer Etiology Cancer Patient Cervical Cessation of life Colorectal Cancer Development Diagnosis Diagnostic Neoplasm Staging EGFR Protein Overexpression Early Diagnosis Epidermal Growth Factor Receptor Epigenetic Process Epithelial Exhibits Frequencies Gene Mutation Genes Genetic Glioblastoma Human Incidence Knock-out Lip structure Malignant - descriptor Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of pancreas Modeling Molecular Mouth Neoplasms Mus Mutation Numbers Oncogene Activation Oral cavity Oral mucous membrane structure Pathway interactions Play Pre-Clinical Model Prevention intervention Process Property Protein Overexpression Purpose Receptor Signaling Relative (related person)Reporting Retinoblastoma Role Signal Pathway Somatic Mutation Squamous cell carcinoma Staging Survival Rate System TP53 gene Testing Therapeutic Agents Tissues Tongue Transgenic Mice Transgenic Organisms Tumor Suppressor Proteins Tumor stage Tumor-Suppressor Gene Inactivation United States base c-erbB-1 Proto-Oncogenes gain of function gain of function mutation human cancer mouse model in vivo Model keratin 14, K14 malignant mouth neoplasm mouse model novel therapeutics oral cavity epithelium tumor tumor initiation tumor progression

项目摘要

Oral cancer is the seventh most common form o_ cancer and causes 8,000 deaths in the United States each year and 128,000 worldwide. Similar to other tumor types, it is widely accepted that the formation of oral cancer is a multi-step process that results from the accumulation of genetic alterations. The high frequency of genetic and epigenetic alterations found in certain genes strongly suggests a causal role in thq development of oral cancer. Our long-term objective is to generate transgenic mice carrying inducibh genetic alterations that closely mimic some of the most common mutations found in human cancer of the or_ cavity. Although a large number of genetic alterations have been reported in oral cancer patients, three different molecular pathways seem to be the major targets of mutations, namely the p53, retinoblastoma (Rb) and Epidermal Growth Factor Receptor (EGFR) signaling pathways. Accordingly, the gene alterations most frequently found in oral cancer include EGFR overexpression, p53 mutations (such as the gain-of- function p53R175H) and inactivation of the INK4a/ARF locus, which functions at least in part as a negative regulator of the Rb pathway. We hypothesize that these mutations that have a high incidence in oral cancer patients play a causal role in the development of cancer of the oral cavity. To test this hypothesis we will use an inducible system to generate mouse models that exhibit p53 mutations, EGFR overexpression or inactivation of the INK4a/ARF locus only in the oral cavity. These models have several advantages over conventional transgenic/knockout models: the mutation can be targeted to a restricted area of the tissue and the moment of tumor initiation can be chosen. Therefore, they will closely mimic the sporadic focal accumulation of somatic mutations found in human tumors. These mouse models will be useful not only to better understand the molecular mechanisms of oral cancer development, but also as preclinical models for testing therapeutic agents for prevention and intervention of oral cancer.

口腔癌是第七种最常见的癌症，在美国每一种癌症导致8000人死亡