Shabelnik M. Expression and function of PKD1 and PKD2 protein kinases in gastric cancer cells

The work is aimed to study the expression, autophosphorylation, function and intracellular localization of serine/threonine protein kinases PKD1 and PKD2 in human gastric cancer. The expression (on mRNA and protein levels), intracellular localization and autophosphorylation of PKD1 and PKD2 were studied in adenocarcinoma gastric cells, adenogen, undifferentiated and signet-ring cell gastric carcinoma, gastric carcinoid. It was shown that the variable expression of PKD1 and PKD2 depends on the morphological variant of gastric cancer. The overall level of expression and activation/autophosphorylation of PKD1 and PKD2 in gastric adenocarcinoma cells correlated with the tumor grade: the poorly differentiated adenocarcinoma had moderate level of total PKD1 and PKD2 expression and activation, the moderately differentiated adenocarcinoma demonstrated high level of PKD1 and PKD2 expression and activation. It was shown that the absence of H. pylori cagA gene in human gastric adenocarcinoma correlated with low level of PKD1/2 autophosphorylation. Moreover, infection of cell lines AGS by H. pylori was accompanied by increased PKD2 expression level, its auto-and transphosphorylation. For the first time it was demonstrated that PKD1 expression and PKD2 overexpression affected the biological characteristics of cells in the model system of gastric cancer cell line AGS. Transfection of PKD1 led to a reduction of PKD2 expression, decrease of cell proliferation, their ability to migration and to form colonies in soft agar. The PKD2 overexpression increased proliferative activity of cells, their migration and colony formation potential.