Molecular cloning and functional analysis of a novel oncogene, cancer-upregulated gene 2 (CUG2)

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Abstract

We examined genome-wide differences in gene expression between tumor biopsies and normal tissues in order to identify differentially regulated genes in tumors. Cancer-upregulated gene 2 (CUG2) was identified as an expressed sequence tag (EST) that exhibits significant differential expression in multiple human cancer types. CUG2 showed weak sequence homology with the down-regulator of transcription 1 (DR1) gene, a human transcription repressor. We found that EGFP-CUG2 fusion proteins were predominantly localized in the nucleus, suggesting their putative role in gene regulation. In addition, CUG2-overexpressing mouse fibroblast cells exhibited distinct cancer-specific phenotypes in vitro and developed into tumors in nude mice. Taken together, these findings suggest that CUG2 is a novel tumor-associated gene that is commonly activated in various human cancers and exhibits high transforming activities; it possibly belongs to a transcription regulator family that is involved in tumor biogenesis.

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Materials and methods

Expression analysis. Expression values of tumor biopsies and normal tissues were obtained from the GeneExpress Oncology Datasuite of Gene Logic Inc., based on the Affymetrix Human Genome U133 array set. Outliers were detected by Principal Component Analysis using MatLab program (The MathWorks, Inc.), and excluded for further analysis. We analyzed the expression profiles of normal and cancer tissue sets from the breast (normal/tumor: 27/55 samples), colon (26/37), esophagus (14/12), kidney

CUG2 is a new gene, up-regulated in tumor tissues

To discover unidentified cancer-causing genes, we used a commercially available oncology database, which contains mRNA expression profiles of around 1200 samples from tumor/normal human tissues using Affymetrix gene chip system. For more reliable analysis, we first ruled out human tissues with small number of sample sets, and then excluded outlier samples from each tissue using Principal Component Analysis. A total of 242 normal and 300 tumor samples originating from 11 different tissues were

Discussion

It is well known that a majority of oncogenes affect cellular signaling processes. The environmental signals are ultimately transferred to transcription factors or to intracellular molecules that activate transcription factors, which induces the change of the transcription pattern of the cell [5], [11]. Therefore, it is not surprising that the major targets of more than 10% of the 50 best-selling drugs approved in the United States are the transcriptional regulatory molecules [12]. This

Acknowledgments

This research was supported in part by the Grants, FG06-2-18 (to S.L.) and FG06-32-2 (to S.S.K.) of the 21C Frontier Functional Human Genome Project from Ministry of Science and Technology of Korea, and R0120050001056102005 from the Basic Research Program of the Korea Science & Engineering Foundation (to S.L.).

We thank Hyun-Ho Chung, Doo Seok Yang, and Sung-Joong Lee for technical support and helpful discussions.

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