The homeobox gene PROX1 is critical for organ development during embryogenesis. The Drosophila homologue, known as prospero has been shown to act as a tumor suppressor by controlling asymmetric cell division of neuroblasts. Likewise, alterations in PROX1 expression and function are associated with a number of human cancers including hematological malignancies, carcinomas of the pancreas, liver and the biliary system, sporadic breast cancer, Kaposiform hemangioendothelioma, colon cancer, and brain tumors. PROX1 is involved in cancer development and progression and has been ascribed both tumor suppressive and oncogenic properties in a variety of different cancer types. However, the exact mechanisms through which PROX1 regulates proliferation, migration, and invasion of cancer cells are by large unknown. This review provides an update on the role of PROX1 in organ development and on its emerging functions in cancer, with special emphasis on the central nervous system and glial brain tumors.
PROX1 is a prospero-related transcription factor that plays a critical role in the development of various organs including the mammalian lymphatic and central nervous systems; it controls cell proliferation and differentiation through different transcription pathwaysand has both oncogenic and tumor-suppressive functions. We investigated PROX1 expression patterns in 56 human astrocytic gliomas of different grades using immunohistochemistry. An average of 79% of cells in World Health Organization Grade IV (glioblastoma, n = 15) and 57% of cells in World Health Organization Grade III (anaplastic astrocytoma, n = 13) were strongly PROX1 positive; low-grade diffuse astrocytomas (Grade II, n = 13) had 21% of cells that were strongly positive; Grade I tumors (n = 15) had 1.5%; and non-neoplastic brain tissue (n = 15) had 3.7% of cells that were PROX1 positive. Double immunolabeling showed that PROX1+ cells in glioblastomas frequently coexpressed early neuronal proteins MAP2 and betaIII-tubulin but not the mature neuronal marker protein NeuN. Analyses of coexpression with proliferation markers suggest that PROX1+ cells have a marginally lower rate of proliferation than other tumor cells but are still mitotically active. We conclude that PROX1 may constitute a useful tool for the diagnosis and grading ofastrocytic gliomas and for distinguishing Grade III and Grade IV tumors from Grade I and Grade II tumors.
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