Zona Pellucida Protein 2 (ZP2) Is Expressed in Colon Cancer and Promotes Cell Proliferation

Abstract

Background: Zona pellucida protein ZP2 has been identified as a new colon tumor biomarker. Its transcripts were specifically expressed in four out of four human colon cancer cell lines and enhanced in about 60% of primary colon cancer tissues when compared to matched healthy ones. ZP2 down-regulation by siRNA led to a decreased proliferation rate, EXOSC5 transcript, cyclin D1 protein level, and ERK1/2 phosphorylation state. Methods: Sensitivity and quantitative expression analysis of ZP2 transcripts in tumor and matched normal colon tissue was performed with respective cDNA preparations. Silencing RNA effects on colon cancer cells were examined by q-PCR, western blot, and proliferation rate experiments. Results: In a significant portion of 69 primary colon tumor samples, the molecule showed a low but specific expression, which revealed a sensitivity value of around 90% and a specificity value of 30% when matched to the respective normal counterparts. Down-regulation of ZP2 protein by siRNA led to a decreased proliferation rate, EXOSC5 and cyclin D1 level, and phosphorylation state of ERK1/2. ZP2 has also been found to be a cell membrane-bound protein. Conclusion: ZP2 shows an enhanced expression level in colon cancer tissue and, thus, can be used as a diagnostic tool, albeit in combination with other biomarkers. Its character as a membrane protein makes ZP2 even a potential target molecule for tumor therapy, especially as it positively affects colon cancer cell proliferation.