Linear and cooperative signaling: roles for Stat proteins in the regulation of cell survival and apoptosis in the mammary epithelium

Nearly all cellular decisions are determined by extracellular signals (eg hormones, growth factors, surface proteins of neighboring cells or extracellular matrix components). These signals are thought to be converted into enzymatic activities and patterns of gene transcription that determine the functions and phenotypes of cells. Signal transduction is controlled by intracellular signaling cascades and the regulation of latent transcription factors. The identification of crucial components, such as specific receptors for signals at the cell surface and linked signal transduction molecules, has led to a basic understanding of, for example, the function of growth factors such as epidermal growth factor or platelet-derived growth factor, hematopoietic cytokines, hormones recognizing receptors coupled to G proteins and steroid hormone action.Although we are still far from a comprehensive picture - especially, the identification of postulated, decisive target genes specifying particular cellular parameters is not sufficiently advanced - the concept has proven valuable. Linear chains of events have been described that link defined extracellular signals to the transcription of individual genes. These insights have nourished the confidence that a network of interactions can be established which will allow very specific modes of interference and the development of new anticancer drugs. These drugs should preferentially target the growth propelling signals in a population of tumor cells with particular genetic abberations, or alternatively activate cellular suicide programs. It is hoped that the principle exemplified by tamoxifen can be emulated. A growth limiting step, in this case the activation of the estrogen receptor, can be identified and exploited for targeted interference. In the most favorable cases, this step is rather restricted to the regulation of the growth of tumor cells, thus its inhibition will cause few undesirable side effects.A prerequisite for such an app