INCREASE IN THE MALIGNANT PROPERTIES OF HUMAN PANCREATIC DUCTAL ADENOCARCINOMA CELLS DUE TO REPRESSION OF HNF4α NUCLEAR RECEPTOR SYNTHESIS

Introduction. Pancreatic ductal adenocarcinoma (PDAC) is notable for its high aggressiveness and low efficiency of diagnostic and treatment approaches. Nuclear receptor HNF4α is one of the possible regulators of the development and differentiation of pancreatic cells which acts as a tumor suppressor in hepatic, intestinal and kidney cells. The role of HNF4α deregulation in PDAC progression is poorly investigated up to date. The aim. The analysis of the influence of HNF4α repression in highly differentiated human PDAC cells CaPan2 on their biological properties determining the malignant potential. Methods. CaPan2 cell cultures with repressed HNF4α synthesis were obtained using RNA-interference. The impact of HNF4α downregulation upon cells growth rate, DNA synthesis intensity, colony formation and directional migration was estimated. Results. HNF4α synthesis inhibition in CaPan2 cell cultures resulted in the significant increase in their in vitro growth rate. This growth acceleration was accompanied by the increase in the fraction of cells that were in S-phase of cell cycle that indicated the intensification of the DNA synthesis. Cells with repressed HNF4α synthesis are characterized by higher ability to form colonies in the conditions of high dilution and to directionally migrate along the gradient of chemoattractant. Conclusion. Repression of HNF4α synthesis in highly differentiated human PDAC cells causes the significant increase in their malignant potential. Thus, HNF4α may act as a tumor suppressor in PDAC cells.