Effects of Parafibromin Expression on the Phenotypes and Relevant Mechanisms in the DLD-1 Colon Carcinoma Cell Line

Abstract

<b>Background:</b> Parafibromin is a protein encoded by the HRPT2 (hyperparathyroidism 2) oncosuppressorgene and its down-regulated expression is involved in pathogenesis of parathyroid, breast, gastric and colorectalcarcinomas. This study aimed to clarify the effects of parafibromin expression on the phenotypes and relevantmechanisms of DLD-1 colon carcinoma cells. <br/><b>Methods</b>: DLD-1 cells transfected with a parafibromin-expressingplasmid were subjected to examination of phenotype, including proliferation, differentiation, apoptosis, migrationand invasion. Phenotype-related proteins were measured by Western blot. Parafibromin and ki-67 expressionwas detected by immunohistochemistry on tissue microarrays. <br/><b>Results</b>: The transfectants showed higherproliferation by CCK-8, better differentiation by electron microscopy and ALP activity and more apoptoticresistance to cisplatin by DNA fragmentation than controls. There was no difference in early apoptosis by annexinV, capase-3 activity, migration and invasion between DLD-1 cells and their transfectants. Ectopic parafibrominexpression resulted in down-regulated expression of smad4, MEKK, GRP94, GRP78, GSK3β-ser9, and Caspase-9.However, no difference was detectable in caspase-12 and -8 expression. A positive relationship was noted betweenparafibromin and ki-67 expression in colorectal carcinoma. <br/><b>Conclusions</b>: Parafibromin overexpression couldpromote cell proliferation, apoptotic resistance, and differentiation of DLD-1 cells.