Functional interleukin-4 receptor and interleukin-2 receptor common gamma chain in human gastric carcinoma: A possible mechanism for cytokine-based therapy

Interleukin (IL)-2 and IL-4 play a critical role in the regulation of the i mmune response. Yet both of the receptors for these cytokines have been fou nd on nonhematopoietic cells, including human gastric carcinoma cell lines and tissue specimens. IL-4 causes GI phase cell cycle arrest of gastric car cinoma; the effect directly correlates with die expression of IL-4 receptor (IL-4R) and is seen within 48 hours after treatment. Cells lacking IL-4R a re unaffected by IL-4. We examined signal transduction pathways employed by IL-Jr that may account for cell cycle arrest of an established human gastr ic carcinoma cell line, CRL 1739. Western blot analysis was performed on CR L 1739 cultured in the presence of IL-4 (500 U/ml). Cells were lysed, prote in extracted, and electroblotted; blots were then probed with murine monocl onal antibodies to specific intracellular proteins. Western blotting of CRL 1739 T vith antiphosphotyrosine antibody ( 4G10) demonstrated multiple (14 0 kDa and 65 kDa) phosphoproteins seen only in IL-4-treated CRL 1739. Immun oprecipitation and blotting of CRL 1739) with specific secondary antibodies demonstrated that the 140 kDa phosphoprotein was IL-4R alpha, the 65 kDa p hosphoprotein was IL-2R gammac, the 130 kDa phosphoprotein was janus kinase (JAK1), and the 116 kDa phosphoprotein was JAK3. Reverse transcription-pol ymerase chain reaction with specific primers demonstrated that multiple hum an gastric tumor specimens expressed IL-4R alpha and IL-2R gammac but did n ot express the leukocyte marker CD45. These results suggest that human gast ric carcinomas may express functional cytokine receptors, including tile IL -2R gammac commonly found in association with the lymphocyte: IL-2R. These receptors may represent novel targets for directing cytokine-based therapy.