Changes in epidermal growth factor receptor expression in human bladder cancer cell lines following interferon-alpha treatment.
OBJECTIVE
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.


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.
Qu
Xian-Jun
XJ
Department of Pharmacology, College of Pharmacy, Shandong University, Jinan, People's Republic of China.
Yang
Jia-Lin
JL
Russell
Pamela J
PJ
Goldstein
David
D
D015536:Down-Regulation; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D016898:Interferon-alpha; D066246:ErbB Receptors