Effects of the endocrine hormone ecdysone on neoplastic tumorigenesis. Thu H. Tran, Rebecca Garrett, Katherine Pfister, Adrian Halme. Cell Biology, University of Virginia School of Medicine, Charlottesville, VA.

   Tumor formation is a multi-factorial process that involves contributions from genetic mutations within tumor cells as well as inputs from surrounding signals. We have begun to examine the role of endocrine hormones in regulating tumor initiation and progression. The endocrine signals ecdysone and juvenile hormone are critical coordinators of normal Drosophila developmental transitions. Using several different neoplastic tumor models, we identified a correlation between the timing of tumor formation in imaginal tissues and the increase of juvenile hormone esterase (Jhe) expression levels. Jhe expression initiates a developmentally important transition in larval hormone signaling where juvenile hormone levels drop and ecdysone signaling begins to rise. Our results suggest that ecdysone could play a role in regulating the development of neoplastic tumors. Thus, we tested the effects of disruption of the ecdysone signaling transduction on neoplastic tumors. Over-expression of dominant negative mutations of the ecdysone receptors leads to drastically reduced growth of tumors with partially restored cell polarity, suggesting that the ecdysone signaling autonomously regulates neoplastic tumorigenesis. Furthermore, we also identified the Wingless signaling pathway, an important regulator of Drosophila development and homeostasis that is regulated by the ecdysone signaling, as a potential mediator of ecdysones effects on neoplastic tumorigenesis. Ongoing experiments are exploring the molecular mechanisms by which the hormone signal ecdysone regulates tumorigenesis.