Phosphatidylinositide 3-kinase/AKT in radiation responses

Histol Histopathol. 2004 Jul;19(3):915-23. doi: 10.14670/HH-19.915.

Abstract

Ionizing or ultraviolet radiation-induced cellular survival signaling pathways induce development of cancer and insensitivity of tumor cells to radiation therapy. Accumulating evidence suggests that the phosphatidylinositide 3-kinase (PI3K)/AKT signal pathway is a major contributor to radioresistance. In many cell types PI3K/AKT signaling is a key cytoprotective response downstream of the EGFR family receptors and mediated carcinogenesis. Cytokines, such as HGF, IGF-I, and IL-6 also protects cells against apoptosis induced by radiation through PI3K/AKT pathway. The mechanics by which PI3K/AKT signaling functions in radiation responses may include its regulation of mitochondrial proteins, transcription factors, translation machinery, and cell-cycle progression. In addition, cross-talk between the PI3K/AKT pathway and mitogen-activated protein kinases, protein kinase A, and protein kinase C signal pathway may also play an important role.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Cell Survival
  • Enzyme Activation / radiation effects
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositol 3-Kinases / radiation effects
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / radiation effects
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / radiation effects
  • Proto-Oncogene Proteins c-akt
  • Radiation*
  • Radiation, Ionizing
  • Reactive Oxygen Species / radiation effects
  • Signal Transduction / radiation effects*
  • Ultraviolet Rays

Substances

  • Proto-Oncogene Proteins
  • Reactive Oxygen Species
  • Phosphatidylinositol 3-Kinases
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt