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Abstract
Seung Min Shin5, 8, Yeun Jun Chung4, 8, Seong Tack Oh1, Hae Myung Jeon1, Lae Jeong Hwang5, Hong Namkoong5, Hyun Kee Kim5, Goang Won Cho5, Soo Young Hur2, Tae Eung Kim2, Youn Soo Lee7, Yong Gyu Park6, Jesang Ko3 and Jin Woo Kim5, 2
1Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
2Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea
3School of Life Sciences and Biotechnology, Korea University, Seoul, Korea
4Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea
5Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea
6Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
7Department of Clinical Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea
Background & Aims: Human cervical cancer oncogene (HCCR-1) has appeared to act as a negative regulator of p53 and contributes to tumorigenesis of various organs including the colon. We identified the HCCR-1 binding protein deleted in polyposis 1 (DP1) and accessed the role of HCCR-1 and DP1 in colon tumorigenesis. Methods: Yeast 2-hybrid was used to identify HCCR-1 interacting proteins. Various molecular biological approaches were used to examine the expression profile of HCCR-1 and DP1, subcellular localization, epitope mapping, the biological role of DP1, and the serum HCCR-1 level. Loss of heterozygosity frequency around DP1 also was examined. Results: We identified that HCCR-1 interacted with DP1. These 2 proteins colocalized in mitochondria but the expression of HCCR-1 showed negative correlation with that of DP1 in colorectal cancer (CRC). DP1 played a tumor-suppressor role in colon tumorigenesis (ie, DP1-transfected RKO cells showed growth inhibition, apoptosis, decreased telomerase activity, and up-regulation of p53). These phenomena were reversed when HCCR-1 was overexpressed. Loss of heterozygosity around the DP1 gene was observed frequently (50%) in CRCs. We examined the use of serum HCCR-1 in CRC patients. The sensitivity of HCCR-1 (76.0%) for detecting CRC was proven to be much higher than that of CA19-9 (32.0%). Conclusions: DP1 plays a tumor-suppressor role in CRC. DP1 and HCCR-1 are supposed to regulate each other negatively by interaction, but further study is required to get better insight into the biological significance of the interaction.
8S.M.S. and Y.J.C. contributed equally to this work
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