Signaling: Previously published studies have used genetic models for investigating the signaling pathways involved in vitamin D growth inhibition and also have demonstrated strong synergistic growth inhibition between vitamin D and genistein on prostatic cells. In addition, his lab's data demonstrate that vitamin D and genistein cooperatively induce p21 proteinand that genistein upregulates vitamin D receptor (VDR) content by modulating protein stability. The effect of genistein on VDR content leads to the hypothesis that one mechanism of synergism between vitamin D and genistein is by enhanced VDR signaling.
Stem Cells: They are developing techniques to isolate cells from the prostate with stem-cell like properties. The lab team has developed an in vitro 3-dimensional culture system and are currently evaluating the effects of different culture conditions on ductal morphogenesis and differentiation. Their goal is to make fully functional prostatic structures in vitro using defined medium.
Epithelial Stromal Interactions: The development of normal and abnormal glandular structures in the prostate is controlled at the endocrine and paracrine levels by reciprocal interactions between epithelium and stroma. His group has developed a method of fresh human prostate tissue acquisition for reproducible isolation of cells from defined histologies and have demonstrated fundamental differences in the inductive capabilities of stromal cells derived from normal or diseased prostatic tissue. Normal stromal cells have no apparent ability to induce epithelial cell growth in a prostate recombination model. Stromal cells derived from benign prostatic hyperplasia induce sharply circumscribed structures. The results support a growing body of work demonstrating that the tumor microenvironment, and specifically, epithelial-mesenchymal interactions are critically important for tumorigenesis. These studies argue that more focused attention should be directed towards the nature of cancer associated stroma. To this end Dr. Cramer and his colleagues plan to compare expression profiles of the normal, BPH and cancer stromal cells to identify candidates for further study using their genetically defined systems.