Targeting the phosphatidylinositol 3-kinase/Akt pathway for enhancing breast cancer cells to radiotherapy

Ke Liang, Weidong Jin, Christiane Knuefermann, Mathias Schmidt, Gordon Mills, K. Kian Ang, Luka Milas, Zhen Fan

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

The phosphatidylinositol 3-kinase (PI-3K)/Akt pathway, regulated by its upstream growth factor receptor tyrosine kinases, plays a critical role in promoting cell proliferation and inhibiting cell death. The aim of this study was to determine whether the PI-3K/Akt activity contributes to the resistance of human breast cancer cells to ionizing radiation and whether inhibition of the PI-3K/Akt pathway could sensitize human breast cancer cells to radiotherapy. To determine a causal relationship between the activity of Akt and radioresistance in human breast cancer cells, MCF7 cells, transfected with constitutively active H-Ras (RadG12V) or constitutively active Akt, were chosen for analysis of the cell clonogenic survival fraction and induction of apoptosis after ionizing radiation. The PI-3K-specific inhibitor LY294002 was used to examine whether inhibition of PI-3K could sensitize these cells to radiation treatment. Our results indicate that the expression of constitutively active Ras (which activated Akt in a PI-3K-dependent manner) and the expression of constitutively active Akt (which caused a PI-3K-independent activation of Akt) each increased cellular resistance to radiation. Inhibition of PI-3K with LY294002 reverted the constitutively active Ras-mediated radioresistance but not the constitutively active Akt-mediated radioresistance. Our data suggest that Akt may be a potential target for enhancing the response to radiotherapy in patients with breast cancer.

Original languageEnglish (US)
Pages (from-to)353-360
Number of pages8
JournalMolecular Cancer Therapeutics
Volume2
Issue number4
StatePublished - Apr 1 2003
Externally publishedYes

Fingerprint

Phosphatidylinositol 3-Kinase
Radiotherapy
Breast Neoplasms
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Ionizing Radiation
Radiation
Growth Factor Receptors
MCF-7 Cells
Protein-Tyrosine Kinases
Cell Survival
Cell Death
Cell Proliferation
Apoptosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Drug Discovery
  • Pharmacology

Cite this

Liang, K., Jin, W., Knuefermann, C., Schmidt, M., Mills, G., Ang, K. K., ... Fan, Z. (2003). Targeting the phosphatidylinositol 3-kinase/Akt pathway for enhancing breast cancer cells to radiotherapy. Molecular Cancer Therapeutics, 2(4), 353-360.

Targeting the phosphatidylinositol 3-kinase/Akt pathway for enhancing breast cancer cells to radiotherapy. / Liang, Ke; Jin, Weidong; Knuefermann, Christiane; Schmidt, Mathias; Mills, Gordon; Ang, K. Kian; Milas, Luka; Fan, Zhen.

In: Molecular Cancer Therapeutics, Vol. 2, No. 4, 01.04.2003, p. 353-360.

Research output: Contribution to journalArticle

Liang, K, Jin, W, Knuefermann, C, Schmidt, M, Mills, G, Ang, KK, Milas, L & Fan, Z 2003, 'Targeting the phosphatidylinositol 3-kinase/Akt pathway for enhancing breast cancer cells to radiotherapy', Molecular Cancer Therapeutics, vol. 2, no. 4, pp. 353-360.
Liang, Ke ; Jin, Weidong ; Knuefermann, Christiane ; Schmidt, Mathias ; Mills, Gordon ; Ang, K. Kian ; Milas, Luka ; Fan, Zhen. / Targeting the phosphatidylinositol 3-kinase/Akt pathway for enhancing breast cancer cells to radiotherapy. In: Molecular Cancer Therapeutics. 2003 ; Vol. 2, No. 4. pp. 353-360.
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