Novel expression patterns of the myc/max/mad transcription factor network in developing murine prostate gland

Purpose: Expression of myc proto-oncogenes and myc-antagonizing mad/mxi gen es typically predominate in proliferating versus differentiating cells, res pectively. C-myc expression in prostate cells is well established but to ou r knowledge that of several recently discovered mad/mxi genes is completely uncharacterized. Such characterization is particularly relevant because mx i 1 is lost or mutated in some human prostate tumors and mouse mxi1-null mu tants show prostatic hyperplasia. Materials and Methods: Developing murine prostatic lobes at select postnata l days 1 to 28 were analyzed by in situ immunohistochemical and in vitro RN A analysis, The expression patterns of the 3 myc genes c-, L- and N-myc, an d the mad1, mxi1 and mad4 genes were studied in most detail with nonradioac tive in situ and immunohistochemical analyses. Results: We describe what is to our knowledge previously unreported express ion of N- and L-myc in the prostate with particularly the latter strongly e xpressed throughout development. High c-myc expression was lost at day 7 wi th re-elevation at day 14, followed by subsequent low expression, represent ing a unique in vivo confirmation of c-myc expression changes seen previous ly in several in vitro differentiation systems. The alternatively spliced w eak and strong repressor mxi1 isoforms showed distinct, partially overlappi ng expression patterns. Of particular interest were continual mad1 and mad4 expression during the proliferative and differentiative phases. Similarly mad1 was evident in proliferating normal prostate cell cultures but not in tumor cell lines, suggesting that mad1 expression in prostate may be clinic ally relevant. Conclusions: Myc network expression in developing mouse prostate is novel a nd does not completely fit previous simpler models of Myc versus Mad expres sion based on other cell types.