Overexpression of PRL-1 and PRL-2 in pancreatic cancer cell lines and tumor samples

270 The PRL phosphatases (which consist of PRL-1, PRL-2 and PRL-3 in humans) have been implicated in cancer cell growth and metastasis, and are currently being validated as biomarkers and therapeutic targets in a variety of tumor types. Using cDNA microarray, we previously identified and reported PRL-1 as being highly upregulated in pancreatic cancer cell lines (Cancer Res 2002. 62:10;2890-6). In addition, mRNA levels of PRL-1, PRL-2, and PRL-3 in a large panel of cell lines have been described recently (Proc AACR 2006;47:[5028]), showing that PRL-2 might also be highly expressed in pancreatic cancer cell lines. Examination of PRL expression at the protein level, however, has remained less explored. We sought to further evaluate the expression of the PRL phosphatases at the protein level in pancreatic cancer cell lines and extend our findings to in situ analysis of pancreatic tumors by using tissue microarray (TMA) technology. As determined by Western blot, we found that PRL-1 and PRL-2, but not PRL-3 were highly expressed in pancreatic cancer cell lines, with expression comparable to that of other cancer cell lines previously described as having high PRL-1 or PRL-2 levels. Focusing on PRL-1 and PRL-2, TMA slides containing 53 tumor samples and 38 normal samples (20 of which were matched adjacent to tumor) were stained using PRL-1 or PRL-2 antibodies. Staining over background of PRL-1 or PRL-2 in adenocarcinoma was moderate to strong for ~40% of the tumors. In contrast over 90% of the normal pancreas counterparts stained negative or weak for both PRL proteins. Our results suggest that PRL-1 and PRL-2 are expressed in a subset of pancreatic tumors and further experiments are being undertaken to determine the role that PRL phosphatases play in the biology of these tumors. This work was supported by a grant from the National Foundation for Cancer Research (NFCR).