HCCR-1-Interacting Molecule "Deleted in Polyposis 1" Plays a Tumor-Suppressor Role in Colon Carcinogenesis

Seung Min Shin, Yeun Jun Chung, Seong Tack Oh, Hae Myung Jeon, Lae Jeong Hwang, Hong Namkoong, Hyun Kee Kim, Goang Won Cho, Soo Young Hur, Tae Eung Kim, Youn Soo Lee, Yong Gyu Park, Jesang Ko, Jin Woo Kim

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2074-2086
Number of pages13
JournalGastroenterology
Volume130
Issue number7
DOIs
Publication statusPublished - 2006 Jul

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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