The suppressive effect was less pro nounced in normally phenotypic ductal cells. In primary pancreatic cancer tissues, SON was overexpressed inhibitor Y-27632 in ductal adenocarcinomas compared with normal duct cells and PanINs. Knockdown of SON induced G2M arrest and apoptosis. SON shuttled between the nucleus and cytoplasm depending on the phase of cell cycle. These results indicate that SON plays a crucial role in the proliferation, survival, and tumorigenicity Inhibitors,Modulators,Libraries of pancreatic cancer cells, thus suggesting that this molecule could be a prime therapeutic molecular target for pancreatic cancer. Our investigation showed that knockdown of MAPK associated molecules suppressed the proliferation of pancreatic cancer cells in vitro to variable degrees.

We found that knockdown of AURKB, CENPA, EBNA1BP2, GOLT1A, KIF11, NEDD4L, SON, TPX2, or WDR5 strongly suppressed the proliferation. AURKB encodes aurora kinase B, which is involved in chromo some segregation and cytokinesis during Inhibitors,Modulators,Libraries mitosis. CENPA encodes centromere protein A, which, by functioning as a replacement for histone H3 in centromeric nucleosomes, plays an essential role in kin etochore formation and functions in cellular mitosis. EBNA1BP2 encodes a ribonucleoprotein, Epstein Barr virus nuclear antigen 1 binding protein 2, which serves as a scaffold for ribosome biogenesis. GOLT1A encodes Golgi transport 1A, which functions as a transporter on the Golgi membrane. KIF11 encodes a microtubule dependent motor protein, kinesin family member 11, which plays a critical role in chromosome Inhibitors,Modulators,Libraries positioning during mitosis.

NEDD4L encodes neural precursor cell expressed, develop mentally down regulated 4 like, an E3 ubiquitin protein lig ase that plays a role in polyubiquitination and proteasomal destruction of SMAD23. TPX2 encodes a homologue of Tpx2 of Xenopus, a binding partner of aurora kinase A that plays a role in microtubule spindle formation. WDR5 encodes WD repeat domain Inhibitors,Modulators,Libraries 5, which binds methylated histone Inhibitors,Modulators,Libraries H3 lysine 4 and is required for recruiting H3K4 methyltransferase. Among these, AURKB, CENPA, KIF11, and TPX2 are involved in functions of the microtubule spindles and kinetochores, which are considered essential for cell mitosis. Because we screened by assaying the effects of knockdown of the MAPK associated genes on in vitro proliferation of pancreatic cancer cells, molecules associated with the microtubules and kinetochores might be selectively represented in our screening.

Interestingly, these microtubule kinetochore associated molecules have already been studied as molecu lar targets in various cancers. Nevertheless, of these MAPK associated molecules, we found that knockdown of SON most remarkably suppressed proliferation, which led us to investigate SON in detail as a candidate molecular target. SON encodes kinase inhibitor MG132 SON, a large protein harboring a serine or arginine rich domain.