Basal Cell Marker p63 and Prostate Stem Cells

摘要

The existence of prostate stem cell capable of giving rise to all the epithelial lineages present in the adult prostate is very controversial. Understanding the stages of cell differentiation in normal prostate epithelium is essential for the identification of the cell type(s) involved in prostate carcinogenesis. The p53-homologue p63 is selectively expressed in the basal cell compartment of a variety of epithelial tissues and p63 deficient mice show severe defects in the development of epithelial organs, including agenesis of the prostate. These findings suggest that p63 is required to maintain a prostate stem cell population. In order to test this hypothesis we will first study p63 expression in the various stages of prostate development in wild type mice by both immunohistochemistry and in situ hybridization (Specific Aim 1). We will also construct chimeric mice by injecting p63+1+ beta-galactosidase positive ES cells into p634- blastocysts (Specific Aim 2) and then analyze the relative contribution of p63+/+ and p63-/- cells to the prostatic epithelium. In the event in which both basal and secretory cells require p63 for development, the results will indicate that both compartments originate from a common p63- positive stem cell.