Role of STAT proteins in c-Src and EGF receptor signaling pathways, proliferation, and tumorigenesis; role of STATs in crosstalk with steroid signaling

Currently, the main research focus of the Silva laboratory is to investigate the role of the transcription factors, STAT5a and STAT5b in the signaling pathways activated in models of breast cancer.  There are three major areas of research in the lab:  (1) Investigation of the molecular mechanism of STAT5 activation in models of c-Src and EGF receptor co-overexpression; (2) The role of the STAT proteins in early models of breast cancer in which the estrogen receptor is expressed; and (3) the biological impact of novel tyrosine and serine phosphorylation sites in the transcriptional activation domain of STAT5b (and STAT5a).  The lab model systems include engineered mouse fibroblast cell lines, a panel of well-characterized human breast cancer cell lines; and primary human breast tumor (and normal) tissue.  A number of molecular tools and techniques with which to study STAT activity and function have been developed in the laboratory and will be used to study this model.  These tools include:  (1) STAT specific antibodies for immunprecipiation and Western blotting; (2) epitope tagged STAT expression vectors for structure/function analysis; (3) luciferase reporter assay; (4) dominant negative and constitutively active forms of STATs for proliferation and tumorigenesis assays; (5) phage display; (6) mRNA analysis by Northern and RT-PCR; (7) chromatin immunoprecipitation (ChIP) assay.  The group's ultimate goal is that these studies will lead to methods and/or reagents that provide novel treatment paradigms for breast cancer.