Oncogenic Signaling in the Adult Prostate-like Accessory Gland Leads to Activation of a Conserved Pro-tumorigenic Program, in the Absence of Proliferation

models for tumorigenesis and metastasis have revealed conserved mechanisms of signaling that are also involved in mammalian cancer. Many of these models use the proliferating tissues of the larval stages of development, when tissues are highly mitotically active, or stem cells are abundant. Fewer tumorigenesis models use adult animals to initiate tumor formation when many tissues are largely terminally differentiated and postmitotic. The accessory glands are prostate-like tissues and a model for some aspects of prostate tumorigenesis using this tissue has been explored. In this model, oncogenic signaling was induced during the proliferative stage of accessory gland development, raising the question of how oncogenic activity would impact the terminally differentiated and postmitotic adult tissue. Here, we show that oncogenic signaling in the adult accessory gland leads to activation of a conserved pro-tumorigenic program, similar to that observed in mitotic larval tissues, but in the absence of proliferation. Oncogenic signaling in the adult postmitotic gland leads to tissue hyperplasia with nuclear anaplasia and aneuploidy through endoreduplication, which increases polyploidy and occasionally results in non-mitotic neoplastic-like extrusions. We compare gene expression changes in our model with that of endocycling prostate cancer cells induced by chemotherapy, which potentially mediate tumor recurrence after treatment. Similar signaling pathways are activated in the gland and endocycling cancer cells, suggesting the adult accessory glands provide a useful model for aspects of prostate cancer progression that do not involve cellular proliferation.