Differentially expressed cDNAs in PLCbeta3-induced tumor suppression in a human endocrine pancreatic tumor cell line: activation of the human mismatch repair protein 3 gene.

Phospholipase Cbeta3 (PLCB3) is located to chromosome 11q13 in the vicinity of the multiple endocrine neoplasia type1 (MEN1) gene and shows loss of expression in some neuroendocrine tumors. Transfection of PLCB3 to neuroendocrine cell lines induces growth suppression and phenotypic alterations, but the mechanisms remain unclear. To investigate the underlying events behind this tumor suppression, we performed an RT-Differential cDNA Display of total RNA from BON-1 (human endocrine pancreatic tumor cell line) transfected with PLCB3 and compared to wild type and BON-1 transfected with vector without insert. PLCB3 transfection resulted in increased expression of 4 genes and decreased of 2. The two inhibited were homologous to S100A3 and Chromogranin A. One of the four activated cDNAs could be identified as human mismatch repair protein 3 mRNA (hMSH3), and another was homologous to TIS/MA-3 mRNA (mouse topoisomerase suppressor inhibited gene/mouse apoptosis gene-3). Differential expression of these genes may contribute to the PLCB3-induced tumor suppression of neuroendocrine tumor cell lines.