Báo cáo y học: Elevated expression of CD30 in adult T-cell leukemia cell lines: possible role in constitutive NF-κB activation

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Báo cáo y học: "Elevated expression of CD30 in adult T-cell leukemia cell lines: possible role in constitutive NF-κB activation"Retrovirology BioMed Central Open AccessResearchElevated expression of CD30 in adult T-cell leukemia cell lines:possible role in constitutive NF-κB activationMasaya Higuchi1, Takehiro Matsuda2, Naoki Mori2, Yasuaki Yamada3,Ryouichi Horie4, Toshiki Watanabe5, Masahiko Takahashi1, Masayasu Oie1and Masahiro Fujii*1Address: 1Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan, 2Division ofMolecular Virology and Oncology, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan, 3Department ofLaboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 825-8501, Japan, 4Fourth Department of InternalMedicine, Faculty of Medicine, Kitasato University, Sagamihara, Kanagawa 228-8555, Japan and 5Laboratory of Tumor Cell Biology, Departmentof Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Minato-ku, Tokyo 108-109, JapanEmail: Masaya Higuchi - mhiguchi@med.niigata-u.ac.jp; Takehiro Matsuda - k028745@med.u-ryukyu.ac.jp; Naoki Mori - n-mori@med.u-ryukyu.ac.jp; Yasuaki Yamada - y-yamada@net.nagasaki-u.ac.jp; Ryouichi Horie - rhorie@med.kitasato-u.ac.jp;Toshiki Watanabe - tnabe@ims.u-tokyo.ac.jp; Masahiko Takahashi - masahiko@med.niigata-u.ac.jp; Masayasu Oie - moie@med.niigata-u.ac.jp;Masahiro Fujii* - fujiimas@med.niigata-u.ac.jp* Corresponding authorPublished: 06 May 2005 Received: 07 February 2005 Accepted: 06 May 2005Retrovirology 2005, 2:29 doi:10.1186/1742-4690-2-29This article is available from: http://www.retrovirology.com/content/2/1/29© 2005 Higuchi et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Human T-cell leukemia virus type 1 (HTLV-1) is associated with the development of adult T-cell leukemia (ATL). HTLV-1 encoded Tax1 oncoprotein activates the transcription of genes involved in cell growth and anti-apoptosis through the NF-κB pathway, and is thought to play a critical role in the pathogenesis of ATL. While Tax1 expression is usually lost or minimal in ATL cells, these cells still show high constitutive NF-κB activity, indicating that genetic or epigenetic changes in ATL cells induce activation independent of Tax1. The aim of this study was to identify the molecules responsible for the constitutive activation of NF-κB in ATL cells using a retroviral functional cloning strategy. Results: Using enhanced green fluorescent protein (EGFP) expression and blasticidin-resistance as selection markers, several retroviral cDNA clones exhibiting constitutive NF-κB activity in Rat-1 cells, including full-length CD30, were obtained from an ATL cell line. Exogenous stable expression of CD30 in Rat-1 cells constitutively activated NF-κB. Elevated expression of CD30 was identified in all ATL lines examined, and primary ATL cells from a small number of patients (8 out of 66 cases). Conclusion: Elevated CD30 expression is considered one of the causes of constitutive NF-κB activation in ATL cells, and may be involved in ATL development. one year of diagnosis. Human T-cell leukemia virus type 1BackgroundAdult T-cell leukemia (ATL) is an extremely aggressive (HTLV-1) infection of CD4+ T-cells is the first step in ATLhuman CD4+ T-cell leukemia (reviewed in [1]). ATL is development. However, this alone is not sufficient for theresistant to chemotherapy and most patients die within development of leukemia because a minority of HTLV-1 Page 1 of 12 (page number not for citation purposes)Retrovirology 2005, 2:29 http://www.retrovirology.com/content/2/1/29infected subjects (approximately 5%) develop ATL on [37,38]. There may be genetic or epigenetic changes that lead to tax-independent NF-κB activation, such as a gainaverage 60–70 years after the infection (reviewed in [2,3]). of function of the NF-κB activating molecule(s) or a lossIn vitro, HTLV-1 transforms primary human CD4+ T-cells of function of the NF-κB regulator(s). The elucidation ofin an interleukin (IL)-2-dependent or an IL-2-independ- the molecular mechanism of NF-κB activation in ATL cellsent manner. HTLV-1 encoded Tax1 protei ...