DOMINANT NEGATIVE ESTROGEN RECEPTORS AND BREAST CANCER

显性负雌激素受体与乳腺癌

• 批准号: 2443203
• 负责人: KIRK E EKENA
• 金额: $ 2.86万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2443203
• 关键词: breast neoplasms; estrogen receptors; genetic manipulation; hormone metabolism

The objective of this research is to develop and investigate a novel method for functional inactivation of estrogen receptor (ER) in estrogen-responsive human breast cancer cells. The approach is based on dominant negative ER mutants which, while inactive on their own, suppress the activity of wildtype ER when they are co-expressed in the same cells. Powerful ER mutants will be generated by replacing the N- and C-terminal transactivation domains with polyalanine tracts and by using the P22 challenge phage system to isolate mutations that result in increased ability of mutant ER to compete for binding to estrogen response element DNA. The relative contributions of competition for binding to the ERE, formation of heterodimers, and interference with ER- specific transcription components to the activity of the dominant negative mutants will be determined. Stably transfected MCF-7 human breast cancer cells producing the dominant negative mutant ERs will be examined for suppression of estrogen-stimulated growth in vitro, and in vivo using athymic nude mice. These studies will provide new insights into ER regulation of gene expression and the proliferation and tumorigenicity of breast cancer cells, and allow evaluation of a novel approach for the extinction of estrogen-dependent breast cancer growth.

本研究的目的是开发和研究一部小说

项目成果

Constitutively active human estrogen receptors containing amino acid substitutions for tyrosine 537 in the receptor protein.

• DOI: 10.1210/mend.10.11.8923465
• 发表时间: 1996-11
• 期刊: Molecular endocrinology
• 作者: Karen E. Weis;K. Ekena;James A. Thomas;G. Lazennec;B. Katzenellenbogen