title: HCCR-1-interacting molecule "deleted in polyposis 1" plays a tumor-suppressor role in colon carcinogenesis.
abstract: OBJECTIVE
  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.
authors.affiliation: Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seung Min
authors.initials: SM
authors.lastname: Shin
authors.forename: Yeun Jun
authors.initials: YJ
authors.lastname: Chung
authors.forename: Seong Tack
authors.initials: ST
authors.lastname: Oh
authors.forename: Hae Myung
authors.initials: HM
authors.lastname: Jeon
authors.forename: Lae Jeong
authors.initials: LJ
authors.lastname: Hwang
authors.forename: Hong
authors.initials: H
authors.lastname: Namkoong
authors.forename: Hyun Kee
authors.initials: HK
authors.lastname: Kim
authors.forename: Goang Won
authors.initials: GW
authors.lastname: Cho
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Hur
authors.forename: Tae Eung
authors.initials: TE
authors.lastname: Kim
authors.forename: Youn Soo
authors.initials: YS
authors.lastname: Lee
authors.forename: Yong Gyu
authors.initials: YG
authors.lastname: Park
authors.forename: Jesang
authors.initials: J
authors.lastname: Ko
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Kim
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D001665:Binding Sites; D015152:Blotting, Northern; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology; D053938:DNA Fragmentation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012494:Sampling Studies; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D011518:Proto-Oncogene Proteins