HCCR-1-interacting molecule "deleted in polyposis 1" plays a tumor-suppressor role in colon carcinogenesis.
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.
Shin
Seung Min
SM
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Chung
Yeun Jun
YJ
Oh
Seong Tack
ST
Jeon
Hae Myung
HM
Hwang
Lae Jeong
LJ
Namkoong
Hong
H
Kim
Hyun Kee
HK
Cho
Goang Won
GW
Hur
Soo Young
SY
Kim
Tae Eung
TE
Lee
Youn Soo
YS
Park
Yong Gyu
YG
Ko
Jesang
J
Kim
Jin Woo
JW
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
D011518:Proto-Oncogene Proteins