The PRL
phosphatases have been implicated in
cancer cell growth and
metastasis in a variety of
tumor types. Using
cDNA microarray, we previously identified and reported PRL-1 as being highly up-regulated in
pancreatic cancer cell lines. In this study, we sought to further evaluate the expression of all three PRL
phosphatases in
pancreatic cancer cell lines and extend our findings to in situ analysis of primary pancreatic
tumors taken directly from patients. Additionally, we determine if
small interfering RNA-mediated knockdown of relevant PRLs confers antitumor effects in
pancreatic cancer cells. Using
oligonucleotide expression arrays,
mRNA levels of PRL-1 and PRL-2 but not PRL-3 were identified as up-regulated in
pancreatic cancer cell lines and
tumor samples taken directly from patients compared with those of normal pancreas. Focusing on PRL-1 and PRL-2, high levels of both
proteins were detected in a subset of
pancreatic cancer cell lines and
tumor samples using Western blotting and immunohistochemistry, respectively.
Small interfering RNA-mediated knockdown of PRL-1 and PRL-2 in combination resulted in a moderate reduction of cellular growth and migration in MIA PaCa-2 and PANC-1 cells. More importantly, knockdown of both PRL-1 and PRL-2 significantly inhibited colony formation of these cells in soft
agar as well as serum-induced Akt phosphorylation. These data support the hypothesis that PRL
phosphatases regulate key pathways involved in
tumorigenesis and
metastasis and that knockdown of both PRL-1 and PRL-2 is required to disrupt PRL
phosphatase function in
pancreatic cancer cells.