Adenoviral vector-mediated augmentation of epidermal growth factor receptor (EGFr) enhances the radiosensitization properties of anti-EGFr treatment in prostate cancer cells.

Academic Article

Abstract

  • PURPOSE: To determine whether an adenoviral vector approach to the augmentation of epidermal growth factor receptor (EGFr) expression results in increased antiproliferative and radiosensitization properties of anti-EGFr antibody therapy in prostate cancer cells. METHODS AND MATERIALS: DU145 and LNCaP human prostate cancer cells were used to test the above question in vitro. An adenoviral vector was utilized to transduce cells with an EGFr transgene (AdEGFr). Immunoblots were performed to measure EGFr expression and EGFr tyrosine phosphorylation. Radiolabeled ligand studies were employed to test binding of epidermal growth factor to EGFr. Scatchard analyses allowed for quantification of the number of EGFrs. Standard immunohistochemistry was performed to assess EGFr expression. Cellular proliferation was assessed after various combinations of treatment. RESULTS: Studies of prostate carcinoma cells infected with AdEGFr demonstrated an increase in EGFr expression. This increase in expression correlated with increased function of EGFr. Specifically, increased EGFr expression also resulted in increased ligand binding, ligand-induced internalization of EGFr, and ligand-induced EGFr tyrosine kinase activity that could be blocked with pre-exposure to IMC-C225 (an anti-EGFr monoclonal antibody). Transduction of the LNCaP cells with AdEGFr did not increase the antiproliferative effects of IMC-C225, but did significantly increase IMC-C225-induced radiosensitization as determined by cell proliferation. CONCLUSIONS: Augmentation of EGFr expression, through an adenoviral vector approach in prostate carcinoma cells, resulted in cells that demonstrated greater IMC-C225-induced radiosensitization compared to cells that were not treated with AdEGFr.
  • Keywords

  • Adenoviridae, Cell Division, Epidermal Growth Factor, ErbB Receptors, Genetic Vectors, Humans, Male, Phosphorylation, Prostatic Neoplasms, Protein-Tyrosine Kinases, Radiation Tolerance, Transduction, Genetic, Tumor Cells, Cultured
  • Digital Object Identifier (doi)

    Author List

  • Bonner JA; Buchsbaum DJ; Rogers BE; Grizzle WE; Trummell HQ; Curiel DT; Fiveash JB; Ove R; Raisch KP
  • Start Page

  • 950
  • End Page

  • 958
  • Volume

  • 58
  • Issue

  • 3