PRECLINICAL MOUSE MODELS: CENTRAL NERVOUS SYSTEM CANCERS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Astrocytic glioma is the most prevalent primary brain tumor in human. Rarely responding to standard tumor therapies, it is one of the most deadly human tumors. The Van Dyke lab recently developed trangenic mouse model for astrocytoma by inactivating the Rb pathway, which occurred in 90% of the human counterpart. This model closely resembles the pathology and molecular pathways of human glioma (see publication). Little is understood about the properties of astrocytes elicited by cancer-promoting lesions in distinct brain microenvironments either in human cases or in our model. The aim of this project is designed to address distinct questions about the morphology, distribution and molecular constituents associated with normal,and tumor-associated astrocytes. We propose to use the techniques devloped in NCMIR to investigate 1 tumor-associated and peritumoral astrocytic morphology, 2 astrocytic distribution and boundaries within tumors and 3 differences in distribution of molecular constituents associated with tumor and normal surrounding areas by large scale mapping. The PI, Dr. Terry Van Dyke has utilized mouse manipulation strategies to study cancer for 16 years. In the course of analyzing the tumor suppressors p53 and pRb, her lab has established several tumor models using transgenic and knock-out strategies.