Shunting Proliferation Signals to Apoptotic Pathways for Treatment of Breast Cancer

摘要

Cells have the remarkable ability of detecting specific external stimuli and translating them into growth, differentiation or death. These responses are mediated by signal transduction pathways such as mitogen- activated protein(MAP) kinase pathways conserved from yeast to man. Because of their roles in regulating cell growth, differentiation and death, improper activation of MAP kinase pathways has implicated in breast cancer and other proliferative diseases. The flow of intracellular signaling information is mediated by a series of protein-protein interactions that often take place on scaffold proteins. Scaffold proteins are postulated to tether together a set of pathway proteins and help them act on each other. The flow of signaling information can be artificially modulated to create a novel input-output relationship by engineering scaffold proteins which recruit a unique set of signaling proteins. This strategy of pathway engineering provides for a novel means to treat diseases caused by signaling defects. The progress of breast cancer is determined by a precise balance between growth signaling and death signaling inside cell. One way to treat breast cancer could be the suppression of growth signaling, the promotion of death signaling or both in cancer cells. Goal in this study is to shunt the growth signal to cell death in breast tumor cells and to study in detail the regulatory mechanisms of MAP kinase signaling by identifying negative regulators.