EGFR-Lung cancer
Anti-EGFR–mediated radiosensitization as a result of augmented EGFR expression

https://doi.org/10.1016/j.ijrobp.2004.01.053Get rights and content

Abstract

Purpose

Elevated epidermal growth factor receptor (EGFR) expression has correlated with a poor prognosis after standard treatment of several malignancies. However, it is not clear whether the absolute level of EGFR expression affects the radiosensitizing properties of anti-EGFR treatments. A better understanding of this question would be helpful for the design of protocols that deliver these treatments. To explore this question, cells (LS174T) that did not display inherent anti-EGFR treatment–induced radiosensitization were selected for studies that could potentially enhance EGFR expression.

Materials and methods

Human colon carcinoma cells (LS174T), which did not show radiosensitization by anti-EGFR treatments, were employed for these studies. (Also, these cells were not responsive to the antiproliferative effects of anti-EGFR treatment.) Using standard transfection techniques (eukaryotic expression vector) as well as an adenoviral construct to enhance EGFR expression, LS174T cells were transduced in a manner that resulted in enhanced expression of EGFR. Subsequently, standard proliferation studies were performed to test the radiosensitizing properties of anti-EGFR treatment (an anti-EGFR monoclonal antibody: IMC-C225).

Results

Studies were undertaken to stably transfect LS174T cells with EGFR. The stable transfectants, LS174T.EGFR cells, were responsive to the antiproliferative effects of anti-EGFR treatment, in contrast to the parent LS174T cells. Similar results were demonstrated when the cells were infected with AdEGFR. Additionally, the LS174T.EGFR cells were responsive to the radiosensitizing properties of anti-EGFR treatment (IMC-C225), whereas the parent cells were not.

Conclusions

Although the level of EGFR expression is of prognostic significance in many tumor models, the response of cells to anti-EGFR treatment alone, or combinations of this treatment with radiation or chemotherapy, depends upon many factors that are not necessarily related to the inherent EGFR expression of the tumor cells. However, the studies reported herein, demonstrate that when LS174T cells were transduced to show increased EGFR expression, they became responsive to the radiosensitizing properties of anti-EGFR treatments.

Keywords

Epidermal growth factor receptor (EGFR)
Transduction
Gene therapy

Cited by (0)

Dr. Bonner occasionally serves as a consultant for Bristol-Myers Squibb Company and ImClone Systems Incorporated.

Supported by R01 CA89297 (J.A.B., D.J.B., K.P.R.), R01 HL67972, PSO CA89019, R01 CA86881, and U19 DK57958 (D.T.C.).

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