Regulation of epidermal growth factor receptor in human colon cancer cell lines by interferon alpha.

Abstract

BACKGROUND AND AIM:

The biology of growth factor receptor expression has implications for receptor specific cancer therapy. In this study, we examined: (a) regulation of epidermal growth factor receptor (EGFR) expression in a panel of 10 human colon cancer cell lines using interferon alpha (IFN-alpha); (b) ability of IFN-alpha to inhibit cell proliferation; and (c) sensitivity of IFN-alpha pretreated cells to EGF.

METHODS:

Cell proliferation was measured both by crystal violet colorimetric and clonogenic assays. Cell surface, intracellular, and/or total cell protein expression of EGFR was assessed by indirect immunofluorescence flow cytometry and/or fluorescein isothiocyanate (FITC)-EGF binding and internalisation flow cytometric assay.

RESULTS:

IFN-alpha treatment upregulated expression of cell surface EGFR in seven of 10 colon cancer cell lines within 16 hours, reaching a peak within 48-96 hours; this was accompanied by transient elevation of intracellular EGFR and marked growth inhibition. IFN-alpha treated cancer cells were still sensitive to EGF proliferative stimulation.

CONCLUSIONS:

Our results indicate that cytostatic concentrations of IFN-alpha can enhance cell surface and intracellular EGFR expression in a proportion of human colon cancer cells. The antiproliferative action of IFN-alpha could not block the signal transduction of the EGF-EGFR pathway. This may have clinical implications for improving treatment based on targeting of EGFR.

• Authors: J-L Yang, X-J Qu, P J Russell, D Goldstein
• Journal: Gut (Gut) Vol. 53 Issue 1 Pg. 123-9 (Jan 2004) ISSN: 0017-5749 [Print] England
• PMID: 14684586 (Publication Type: Journal Article)

Chemical References

• Interferon-alpha
• Neoplasm Proteins
• Epidermal Growth Factor
• ErbB Receptors

Topics

• Cell Division (drug effects)
• Colonic Neoplasms (metabolism, pathology)
• Dose-Response Relationship, Drug
• Epidermal Growth Factor (pharmacology)
• ErbB Receptors (drug effects, metabolism)
• Humans
• Interferon-alpha (antagonists & inhibitors, pharmacology)
• Neoplasm Proteins (drug effects, metabolism)
• Tumor Cells, Cultured
• Up-Regulation (drug effects)