NOVEL EXPRESSION PATTERNS OF THE MYC/MAX/MAD TRANSCRIPTION FACTOR NETWORK IN DEVELOPING MURINE PROSTATE GLAND

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Abstract
Expression of myc proto-oncogenes and myc-antagonizing mad/mxi genes typically predominate in proliferating versus differentiating cells, respectively. C-myc expression in prostate cells is well established but to our knowledge that of several recently discovered mad/mxi genes is completely uncharacterized. Such characterization is particularly relevant because mxi1 is lost or mutated in some human prostate tumors and mouse mxi1-null mutants show prostatic hyperplasia.Developing murine prostatic lobes at select postnatal days 1 to 28 were analyzed by in situ immunohistochemical and in vitro RNA analysis. The expression patterns of the 3 myc genes c-, L- and N-myc, and the mad1, mxi1 and mad4 genes were studied in most detail with nonradioactive in situ and immunohistochemical analyses.We describe what is to our knowledge previously unreported expression of N- and L-myc in the prostate with particularly the latter strongly expressed throughout development. High c-myc expression was lost at day 7 with re-elevation at day 14, followed by subsequent low expression, representing a unique in vivo confirmation of c-myc expression changes seen previously in several in vitro differentiation systems. The alternatively spliced weak and strong repressor mxi1 isoforms showed distinct, partially overlapping 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 clinically relevant.Myc network expression in developing mouse prostate is novel and does not completely fit previous simpler models of Myc versus Mad expression based on other cell types.