Changes in Epidermal Growth Factor Receptor Expression in Human Bladder Cancer Cell Lines Following Interferon-Alpha Treatment

J Urol. 2004 Aug;172(2):733-8. doi: 10.1097/01.ju.0000130751.83953.55.

Abstract

Purpose: We examined the regulation of epidermal growth factor (EGF) receptor (EGFR) expression in human bladder cancer cell lines by interferon-alpha (IFN-alpha), the ability of IFN-alpha to inhibit cell proliferation and the sensitivity of IFN-alpha pretreated cells to EGF.

Materials and methods: Cell proliferation was determined using crystal violet colorimetric and clonogenic assays. EGFR expression was measured by flow cytometry using specific antibody or ligand binding approaches.

Results: After IFN-alpha (100 IU/ml) treatment cell surface EGFR expression was upregulated in 6 of 11 and down-regulated in 2 of 11 bladder cancer cell lines. The over expression of cell surface EGFR peaked within 48 to 96 hours and increased by 35% to 241% in individual cell lines. High level cell surface EGFR correlated with intracellular EGFR expression. Cell growth inhibition by IFN-alpha coexisted with EGFR over expression in the 6 lines. IFN-alpha treated cells remained sensitive to EGF treatment.

Conclusions: IFN-alpha transiently up-regulates EGFR expression and inhibits in vitro growth in some human bladder cancer cells. IFN-alpha does not prevent EGFR from binding EGF or signal transduction via the EGF-EGFR pathway. This may have clinical implications for improving treatment based on EGFR targeting in select patients with bladder cancer.

MeSH terms

  • Down-Regulation
  • ErbB Receptors / drug effects*
  • ErbB Receptors / metabolism*
  • Flow Cytometry
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Interferon-alpha / pharmacology*
  • Interferon-alpha / therapeutic use
  • Signal Transduction / physiology
  • Time Factors
  • Tumor Cells, Cultured
  • Up-Regulation
  • Urinary Bladder Neoplasms / metabolism*

Substances

  • Interferon-alpha
  • ErbB Receptors