The developmental biology of brain tumors.

Published

Journal Article (Review)

Tumors of the central nervous system (CNS) can be devastating because they often affect children, are difficult to treat, and frequently cause mental impairment or death. New insights into the causes and potential treatment of CNS tumors have come from discovering connections with genes that control cell growth, differentiation, and death during normal development. Links between tumorigenesis and normal development are illustrated by three common CNS tumors: retinoblastoma, glioblastoma, and medulloblastoma. For example, the retinoblastoma (Rb) tumor suppressor protein is crucial for control of normal neuronal differentiation and apoptosis. Excessive activity of the epidermal growth factor receptor and loss of the phosphatase PTEN are associated with glioblastoma, and both genes are required for normal growth and development. The membrane protein Patched1 (Ptc1), which controls cell fate in many tissues, regulates cell growth in the cerebellum, and reduced Ptc1 function contributes to medulloblastoma. Just as elucidating the mechanisms that control normal development can lead to the identification of new cancer-related genes and signaling pathways, studies of tumor biology can increase our understanding of normal development. Learning that Ptc1 is a medulloblastoma tumor suppressor led directly to the identification of the Ptc1 ligand, Sonic hedgehog, as a powerful mitogen for cerebellar granule cell precursors. Much remains to be learned about the genetic events that lead to brain tumors and how each event regulates cell cycle progression, apoptosis, and differentiation. The prospects for beneficial work at the boundary between oncology and developmental biology are great.

Full Text

Cited Authors

  • Wechsler-Reya, R; Scott, MP

Published Date

  • January 2001

Published In

Volume / Issue

  • 24 /

Start / End Page

  • 385 - 428

PubMed ID

  • 11283316

Pubmed Central ID

  • 11283316

Electronic International Standard Serial Number (EISSN)

  • 1545-4126

International Standard Serial Number (ISSN)

  • 0147-006X

Digital Object Identifier (DOI)

  • 10.1146/annurev.neuro.24.1.385

Language

  • eng