Suppression of anchorage-independent growth by expression of the ataxia-telangiectasia group D complementing gene, ATDC Yoshio Hosoi a,b, * , Leon N. Kapp b , John P. Murnane b,c , Yoshihisa Matsumoto a , Atsushi Enomoto a , Tetsuya Ono d , Kiyoshi Miyagawa a a Department of Radiation Research, Faculty of Medicine, University of Tokyo, Tokyo 113-0033, Japan b Laboratory of Radiobiology and Environmental Health, University of California, San Francisco, San Francisco, CA 94103, USA c Radiation Oncology Research Laboratory, University of California, San Francisco, San Francisco, CA 94103, USA d Department of Radiation Research, Tohoku University School of Medicine, Sendai 980-8575, Japan Received 19 July 2006 Available online 28 July 2006 Abstract The ataxia-telangiectasia group D complementing gene, ATDC, is located at 11q23, where loss of heterozygosity (LOH) is frequently observed in many kinds of cancers including breast cancer. Underexpression of ATDC in breast and prostate cancer has been reported using serial analysis of gene expression (SAGE) and DNA microarray analysis. We previously reported that SV-40-transformation down-regulates the expression of ATDC. In the present study, we investigated the roles of ATDC in carcinogenesis. First, we investigated the expression of ATDC in 11 cancer cell lines. No detectable transcript was observed in 4 tumor cell lines, and no ATDC protein was detected in 8 tumor cell lines. We transfected ATDC expression vector into Saos-2 and BT-549 that lacked detectable mRNA and protein expression of ATDC. Colony-forming efficiency in soft agar was significantly suppressed in all of the ATDC transfectants. These results suggest that suppressed ATDC expression is associated with malignant phenotype. Ó 2006 Elsevier Inc. All rights reserved. Keywords: ATDC; LOH; 11q23; Suppressor oncogene; Carcinogenesis; Transformation A candidate gene for ataxia-telangiectasia (AT) group D (ATDC) has been cloned in 1992 [1]. AT is an autosomal recessive human genetic disease characterized by immuno- logical deficiencies, neurological degeneration, develop- mental abnormalities, and an increased risk of cancer [2]. Cells from AT patients show hyper-sensitivity to ionizing radiation, radioresistant DNA synthesis, elevated recombi- nation, cell cycle abnormalities, and aberrant cytoskeletal organization [2]. ATDC partially restores resistance to ion- izing radiation in cells derived from AT patients, although it does not affect radioresistant DNA synthesis [3]. The ATDC gene is located at 11q23 and is closely linked to THY1 and D11S528 [1]. ATDC is likely to be a member of a gene family whose proteins are characterized by zinc finger and leucine zipper motifs [4]. Recently ATDC has been reported to be a member of tripartite motif (TRIM) protein family, which is characterized by three zinc-binding domains, a RING, a B-box type 1, and a B-box type 2, fol- lowed by a coiled-coil region [5–7]. The ATDC protein physically interacts with the intermediate-filament protein vimentin, which is a protein kinase C substrate, and with hPKCI-1, which is an inhibitor of protein kinase C [8,9]. We previously reported that SV-40-transformation affects the expression of ATDC [10]. Because the large T antigen of SV-40 binds with the products of suppressor oncogenes such as p53 and the retinoblastoma gene (RB) [11,12], the downregulation of ATDC expression, and the change in the splicing pattern observed in SV-40-trans- formed cells might have relevance to cellular transforma- tion [10]. Furthermore, high frequencies of loss of 0006-291X/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.bbrc.2006.07.115 * Corresponding author. Fax: +81 3 5841 3013. E-mail address: hosoi@m.u-tokyo.ac.jp (Y. Hosoi). www.elsevier.com/locate/ybbrc Biochemical and Biophysical Research Communications 348 (2006) 728–734 BBRC