Journal of Neuro-Oncology

, Volume 51, Issue 3, pp 245–264

Mitogenic Signaling and the Relationship to Cell Cycle Regulation in Astrocytomas

  • Arnaud Besson
  • V. Wee Yong
Article

DOI: 10.1023/A:1010657030494

Cite this article as:
Besson, A. & Wee Yong, V. J Neurooncol (2001) 51: 245. doi:10.1023/A:1010657030494

Abstract

The activity and regulation of a number of mitogenic signaling pathways is aberrant in astrocytomas, and this is thought to play a crucial role in the development of these tumors. The cascade of events leading to the formation and the progression from low-grade to high-grade astrocytomas is well characterized. These events include activating mutations, amplification, and overexpression of various growth factor receptors (e.g. epidermal growth factor receptor (EGFR), platelet derived growth factor receptor (PDGFR), c-Met), signaling intermediates (e.g. Ras and Protein kinase C (PKC)), and cell cycle regulatory molecules (e.g. mouse double minute-2 (Mdm2), cyclin-dependent kinase-4 (CDK4), and CDK6), that positively regulate proliferation and cell cycle progression. Inactivating mutations and deletions of signaling and cell cycle regulatory molecules that negatively regulate proliferation and cell cycle progression (e.g. p53, p16/INK4a, p14/ARF, p15/INK4b, retinoblastoma protein (Rb), and Phosphatase and tensin homologue deleted from chromosome 10 (PTEN)) also participate actively in the development of the transformed phenotype. Several mitogenic pathways are also stimulated via an autocrine loop, with astrocytoma cells expressing both the receptors and the respective cognate ligand. Due to the multitude of factors involved in astrocytoma pathogenesis, attempts to target a single pathway have not given satisfactory results. The simultaneous targeting of several pathways or the targeting of signaling intermediates, such as Ras or PKC, situated downstream of many growth factor receptor signaling pathways may show more efficacy in astrocytoma therapy. We will give an overview of how the combination of these aberrations drive astrocytoma cells into a relentless proliferation and how these signaling molecules may constitute relevant therapeutic targets.

PDGFREGFRPKCcell cycle regulationRasintegrinPTEN/MMAC1/TEP1

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Arnaud Besson
    • 1
  • V. Wee Yong
    • 1
  1. 1.Departments of Oncology and Clinical NeurosciencesUniversity of CalgaryCanada