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The Cellular Amount of the Common -Chain Influences Spontaneous or Induced Cell Proliferation¹

Stefania Amorosi^*, Ilaria Russo^*, Giada Amodio^*, Corrado Garbi, Laura Vitiello^,, Loredana Palamaro^*, Marsilio Adriani^*, Ilaria Vigliano^* and Claudio Pignata^2,*

^* Department of Pediatrics, Department of Cellular and Molecular Biology, and Pathology "Federico II" University, Naples, Italy; and Department of Medical Science and Rehabilitation, Instituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Rome, Italy

Mutations of the IL2RG encoding the common -chain (_c) lead to the X-linked SCID disease. Gene correction through ex vivo retroviral transduction restored the immunological impairment in the most of treated patients, although lymphoproliferative events occurred in five of them. Even though in two cases it was clearly documented an insertional mutagenesis in LMO2, it is conceivable that _c could have a role per se in malignant lymphoproliferation. The _c is a shared cytokine receptor subunit, involved also in growth hormone (GH) receptor signaling. Through short interfering RNA or using X-linked SCID B lymphoblastoid cell lines lacking _c, we demonstrate that self-sufficient growth was strongly dependent on _c expression. Furthermore, a correlation between _c amount and the extent of constitutive activation of JAK3 was found. The reduction of _c protein expression also reduced GH-induced proliferation and STAT5 nuclear translocation in B lymphoblastoid cell lines. Hence, our data demonstrate that _c plays a remarkable role in either spontaneous or GH-induced cell cycle progression depending on the amount of protein expression, suggesting a potential role as enhancing cofactor in lymphoproliferation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Ministero dell’Università e della Ricerca Scientifica e Tecnologica, Progetto di Rilevante Interesse Nazionale 2006, and by Ministero della Salute-Roma and Regione Campania, Legge 5.

² Address correspondence and reprint requests to Dr. Claudio Pignata, Professor of Pediatrics, Department of Pediatrics, Unit of Immunology, "Federico II" University, via S. Pansini 5-80131, Naples, Italy. E-mail address: pignata{at}unina.it

³ Abbreviations used in this paper: _c, common -chain; GH, growth hormone; GHR, GH receptor; BCL, B lymphoblastoid cell line; siRNA, small interfering RNA; X-SCID, X-linked SCID.

⁴ The online version of this article contains supplemental material.