Abstract
Unregulated or increased expression of epidermal growth factor receptor (EGF-R) is a common event in neoplastic transformation; modulation of such a receptor by physiological agents could be, therefore, of clinical interest. We have studied the binding ability, the availability at cell surface, and the synthesis of EGF-R in the A431 and KB human epidermoid cancer cell lines after treatment with recombinant α-interferon (IFN-α). After 48 h of treatment, IFN-α induces, in both cell lines, growth inhibition and enhances class I major histocompatibility HLA complex expression, which is a common marker of IFN action. [125I]EGF total binding assessed after 48 h of treatment with IFN-α shows a dose-dependent upregulation of EGF-R binding capacity. Saturation plots of the binding data show that IFN-α treatment does not dramatically alter the affinity of the EGF-R and indicate that IFN-α only increases the number of low affinity receptors. We show that this effect is due to a specific increase in the synthesis of the receptor protein, as assessed by immunoprecipitation of [35S]methionine-labeled cell extracts. Electron microscopy analysis has confirmed an increase of EGF-R proteins at cell surface without major changes in the morphology of the cells. Taken together, these results indicate that IFN-α consistently induces both the binding capacity and the synthesis of EGF-R in human epidermoid cancer cells and suggest the use of such a mechanism for new anticancer therapies.
| Original language | English |
|---|---|
| Pages (from-to) | 1294-1299 |
| Number of pages | 6 |
| Journal | Cancer Research |
| Volume | 51 |
| Issue number | 4 |
| Publication status | Published - Feb 15 1991 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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Upregulation of epidermal growth factor receptor induced by α-interferon in human epidermoid cancer cells. / Budillon, Alfredo; Tagliaferri, Pierosandro; Caraglia, Michele; Torrisi, Maria Rosaria; Normanno, Nicola; Iacobelli, Stefano; Palmieri, Giovannella; Stoppelli, Maria Patrizia; Frati, Luigi; Bianco, Angelo Raffaele.
In: Cancer Research, Vol. 51, No. 4, 15.02.1991, p. 1294-1299.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Upregulation of epidermal growth factor receptor induced by α-interferon in human epidermoid cancer cells
AU - Budillon, Alfredo
AU - Tagliaferri, Pierosandro
AU - Caraglia, Michele
AU - Torrisi, Maria Rosaria
AU - Normanno, Nicola
AU - Iacobelli, Stefano
AU - Palmieri, Giovannella
AU - Stoppelli, Maria Patrizia
AU - Frati, Luigi
AU - Bianco, Angelo Raffaele
PY - 1991/2/15
Y1 - 1991/2/15
N2 - Unregulated or increased expression of epidermal growth factor receptor (EGF-R) is a common event in neoplastic transformation; modulation of such a receptor by physiological agents could be, therefore, of clinical interest. We have studied the binding ability, the availability at cell surface, and the synthesis of EGF-R in the A431 and KB human epidermoid cancer cell lines after treatment with recombinant α-interferon (IFN-α). After 48 h of treatment, IFN-α induces, in both cell lines, growth inhibition and enhances class I major histocompatibility HLA complex expression, which is a common marker of IFN action. [125I]EGF total binding assessed after 48 h of treatment with IFN-α shows a dose-dependent upregulation of EGF-R binding capacity. Saturation plots of the binding data show that IFN-α treatment does not dramatically alter the affinity of the EGF-R and indicate that IFN-α only increases the number of low affinity receptors. We show that this effect is due to a specific increase in the synthesis of the receptor protein, as assessed by immunoprecipitation of [35S]methionine-labeled cell extracts. Electron microscopy analysis has confirmed an increase of EGF-R proteins at cell surface without major changes in the morphology of the cells. Taken together, these results indicate that IFN-α consistently induces both the binding capacity and the synthesis of EGF-R in human epidermoid cancer cells and suggest the use of such a mechanism for new anticancer therapies.
AB - Unregulated or increased expression of epidermal growth factor receptor (EGF-R) is a common event in neoplastic transformation; modulation of such a receptor by physiological agents could be, therefore, of clinical interest. We have studied the binding ability, the availability at cell surface, and the synthesis of EGF-R in the A431 and KB human epidermoid cancer cell lines after treatment with recombinant α-interferon (IFN-α). After 48 h of treatment, IFN-α induces, in both cell lines, growth inhibition and enhances class I major histocompatibility HLA complex expression, which is a common marker of IFN action. [125I]EGF total binding assessed after 48 h of treatment with IFN-α shows a dose-dependent upregulation of EGF-R binding capacity. Saturation plots of the binding data show that IFN-α treatment does not dramatically alter the affinity of the EGF-R and indicate that IFN-α only increases the number of low affinity receptors. We show that this effect is due to a specific increase in the synthesis of the receptor protein, as assessed by immunoprecipitation of [35S]methionine-labeled cell extracts. Electron microscopy analysis has confirmed an increase of EGF-R proteins at cell surface without major changes in the morphology of the cells. Taken together, these results indicate that IFN-α consistently induces both the binding capacity and the synthesis of EGF-R in human epidermoid cancer cells and suggest the use of such a mechanism for new anticancer therapies.
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M3 - Article
VL - 51
SP - 1294
EP - 1299
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 4
ER -