Role of EGFR Family and Integrin Crosstalk in Breast Cancer Progression

EGFR 家族和整合素串扰在乳腺癌进展中的作用

基本信息

批准号：
8381358
负责人：
William Muller
金额：
$ 19.16万
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：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8381358
关键词：
1-Phosphatidylinositol 3-Kinase 8p11 AKT1 gene AKT2 gene Acceleration Address Alleles Anchorage-Independent Growth Binding Sites Bypass C-terminal Cell Culture System Cell Proliferation Clinical Trials Collaborations Complement Coupled Coupling Data Set Development Dominant-Negative Mutation Embryo Ensure Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Epithelial Epithelial Cells Event Exhibits Family Family member Funding Gefitinib Gene Expression Genes Genetic Germ Lines Growth Factor Receptors Human Instruction Integrin Signaling Pathway Integrins Internal Ribosome Entry Site Knock-in Mouse Knock-out Laboratories Link Malignant - descriptor Mammary Neoplasms Mammary Tumorigenesis Mammary gland Measurement Mediating Metabolic Metastatic to Modeling Molecular Mouse Mammary Tumor Virus Mouse Strains Mus Mutate Neoplasm Metastasis Oncogenes PTEN gene Pathway interactions Penetrance Phenotype Phenylalanine Play Property Protein Tyrosine Kinase Proteins Proto-Oncogene Proteins c-akt RNA Interference Recruitment Activity Regulation Relative (related person)Role Signal Pathway Signal Transduction Signaling Molecule Testing Transcriptional Regulation Transgenic Mice Transgenic Organisms Treatment Efficacy Tumor Suppressor Genes Tumor Suppressor Proteins Up-Regulation adapter protein base comparative cytosolic receptor in vivo inhibitor/antagonist insight lapatinib malignant breast neoplasm malignant phenotype mammary epithelium mouse model mutant novel promoter protein function recombinase synergism therapeutic target tumor tumor growth tumor initiation tumor progression vector

项目摘要

PROJECT SUIVIMARY (See Instructions): The progression of a primary mammary epithelial cell to the malignant phenotype is thought to involve multiple genetic events including the activation of dominant acting oncogenes and the loss of specific tumor suppressor genes. Of relevance to this proposal is the observation that activation of certain tyrosine kinases has been implicated in the malignant progression of a significant proportion of human breast cancers. Studies by many laboratories suggest that activation ofthe PI-3K signaling cascade plays a critical role in mammary tumor progression. The principle objective of this proposal is to elucidate the relative contribution of the EGFR family in activation of the PI-3K signaling cascade. To accomplish this objective, we plan to exploit two well characterized transgenic mouse models expressing either ErbB2 under the transcriptional control of the MMTV promoter (NDL) or under its own transcriptional control (ErbB2KI). In particular we plan to assess the relative contribution of ErbBS and its coupled downstream signaling molecules including PI-3K, Aktl and Akt2. Finally, we also will examine the in vivo role of Rab25 and its effector Rab coupling protein (RCP) in ErbB2 mammary tumor progression

SUIVIMARY 项目（参见说明）：原代乳腺上皮细胞向恶性表型的进展被认为涉及多种遗传事件，包括显性作用癌基因的激活和特定肿瘤的丧失抑制基因。与该提议相关的是观察到某些酪氨酸激酶的激活与很大一部分人类乳腺癌的恶性进展有关。许多实验室的研究表明，PI-3K 信号级联的激活在乳腺肿瘤进展。该提案的主要目标是阐明相对贡献 EGFR 家族在 PI-3K 信号级联激活中的作用。为了实现这一目标，我们计划利用两种经过充分表征的转基因小鼠模型，在转录条件下表达 ErbB2 MMTV 启动子 (NDL) 的控制或其自身的转录控制 (ErbB2KI)。我们特别计划评估 ErbBS 及其偶联的下游信号分子（包括 PI-3K）的相对贡献， Aktl 和 Akt2。最后，我们还将研究 Rab25 及其效应子 Rab 偶联蛋白的体内作用 (RCP) 在 ErbB2 乳腺肿瘤进展中的作用