Small interfering RNA-mediated knockdown of PRL phosphatases results in altered Akt phosphorylation and reduced clonogenicity of pancreatic cancer cells

Molecular Cancer Therapeutics
Bret J StephensDaniel D Von Hoff

Abstract

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 ...Continue Reading

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