The Regulation of Lactogenic Differentiation in Mammary Epithelial Cells by Ras-Dependent and -Independent Signal Transduction
Abstract
Epidermal growth factor (EGF) stimulation of mammary epithelial cells (MECs) inhibits differentiation and apoptosis. Excess activation of signaling pathways downstream of the EGF receptor has been directly linked to breast cancer development and chemotherapeutic resistance. Therefore, the dissection of these pathways in normal MECs is critical to the understanding of signaling events that impact breast cancer outcome. HC11 mouse MECs differentiate in response to lactogenic hormone resulting in expression of milk proteins including beta-casein. Previous studies have shown that EGF blocks differentiation through activation of the Ras/Mek/Erk and the PI-3-K pathway. Therefore, specific chemical inhibitors of signal transduction pathways, activated Ras (RasV12), dominant negative-Ras (DN-RasN17), dominant negative-Akt adenovirus(DN-Akt-adeno) and a conditionally active-Akt (CA-Akt) were used to analyze the role of the Ras and PI-3-K pathway in blocking HC11 lactogenic differentiation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 06, 2006
- Accession Number
- AD1014506
Entities
People
- Traci Galbaugh
Organizations
- Uniformed Services University of the Health Sciences