Dr. Bradford's research interests focus on hormone/ growth factor signaling and the regulation of gene transcription. Specifically, his laboratory is studying the role of fibroblast growth factors (FGFs) and Ets transcription factors in the regulation of prolactin gene expression and pituitary tumorigenesis. FGFs are members of a family of polypeptides that play a critical role in development, embryogenesis, angiogenesis and in the regulation of growth, differentiation, motility and survival of cells. Several FGFs have been identified as oncogenes and are implicated in the formation and progression of tumors in a variety of tissues, including breast, prostate, skin, ovary and pituitary. FGFs stimulate prolactin synthesis and secretion and the oncogenic FGF-4 is expressed in human prolactinomas, resulting in formation of aggressive, invasive tumors. Thus, FGFs may play a critical role in the development and pathogenesis of pituitary cancer, but the mechanism of action and components of the FGF signaling pathway remain to be elucidated. Regulation of the prolactin gene provides a physiologically relevant system in which to define and characterize FGF response elements and mediators of FGF signaling and the role of FGFs in tumorigenesis.
The laboratory is also investigating the role of selective protein kinase C (PKC) isoforms in the modulation of cell growth and death in endometrial cancer. In the endometrium, apoptosis plays a critical role in normal menstrual cycle physiology and is regulated in response to estrogen and progesterone. Aberrant apoptosis is observed in dysfunctional uterine bleeding and upon progression from endometrial hyperplasia through atypia to adenocarcinoma. Thus, changes in apoptosis may be an early morphological indicator of progressively abnormal endometrial growth. Differential over-expression of PKC isoforms has been linked to the proliferative potential of endometrial cancer cell lines and may be important in tumor pathogenesis. However, little is known regarding the molecular mechanisms underlying PKC modulation of proliferation and apoptosis in the endometrium.