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HCCR-1–Interacting Molecule “Deleted in Polyposis 1” Plays a Tumor-Suppressor Role in Colon Carcinogenesis

2018-05-16 21:13
Shin, S. M., Chung, Y. J., Oh, S. T., Jeon, H. M., Hwang, L. J., Namkoong, H., ... & Lee, Y. S. (2006). HCCR-1–interacting molecule “deleted in polyposis 1” plays a tumor-suppressor role in colon carcinogenesis. Gastroenterology, 130(7), 2074-2086.

IF(2014) : 16.716


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.