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J Thorac Cardiovasc Surg 2000;119:10-020
© 2000 Mosby, Inc.

GENERAL THORACIC SURGERY

FUNCTIONAL INTERLEUKIN 4 RECEPTOR AND INTERLEUKIN 2 RECEPTOR COMMON -CHAIN ON HUMAN NON–SMALL CELL LUNG CANCERS: NOVEL TARGETS FOR IMMUNE THERAPY

From the Department of Molecular Oncology, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, Calif.

Supported by an American Cancer Society Career Development Award (R. E.) and by a research grant from Viasoft Corporation, Phoenix, Arizona.

Address for reprints: Richard Essner, MD, Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA 90404 (E-mail: essnerr{at}jwci.org).

Objective: The interleukin 4 receptor has been demonstrated on the surface of human non–small cell lung carcinoma cell lines and tumor specimens. Interleukin 4 causes G1-phase cell-cycle arrest of non–small cell lung cancer cell lines expressing the interleukin 4 receptor; the effect directly correlates with the expression of the interleukin 4 receptor and is seen within 48 hours after treatment. We examined signal transduction pathways used by the interleukin 4 receptor that may account for growth arrest of the cell line LUst but had no effect on another non–small cell lung cancer cell line, SK-MES-1.
Methods: Western blot analysis was performed on both LUst and SK-MES-1 cell lines cultured in the presence of interleukin 4 (500 U/mL). Cells were lysed, protein extracted, and electroblotted; blots were then probed with murine monoclonal antibodies to specific intracellular proteins.
Results: Western blotting of the cell lines with antiphosphotyrosine antibody (4G10) demonstrated multiple (140 kd, 100-130 kd, and 65 kd) phosphoproteins seen only in the interleukin 4–treated LUst cell line and not observed in the SK-MES-1 cell lines. Immunoprecipitation and blotting of the LUst cell line with specific secondary antibodies demonstrated that the 140-kd phosphoprotein was the interleukin 4 receptor, the 130-kd phosphoprotein was Janus kinase 1, the 116-kd phosphoprotein was Janus kinase 3, and the 65-kd phosphoprotein was the interleukin 2 receptor -chain. Specific binding was not observed in the non–small cell lung cancer cell line SK-MES-1, suggesting that a functional interleukin receptor -chain was not present. Southern blotting with complementary DNA probes to interleukin 2 receptor -chain confirmed the absence of this receptor on cell line SK-MES-1.
Conclusions: These results suggest that non–small cell lung cancer cells may express functional cytokine receptors, including the interleukin 2 receptor -chain commonly found in association with the lymphocyte interleukin 2 receptor. These receptors may be novel targets for directing cytokine-based immune therapy.

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