RETINOIC ACID RECEPTOR-BETA REGULATES GROWTH AND DIFFERENTIATION IN HUMAN PANCREATIC-CARCINOMA CELLS

Background & Aims: Retinoic acid receptor beta (RAR beta) expression i s lost or decreased during malignant transformation in human pancreati c adenocarcinoma. The aim of this study was to evaluate the role of RA R beta expression in the propagation of a malignant phenotype in human pancreatic carcinoma cells. Methods: Overexpression of RAR beta in th e human pancreatic carcinoma cell line DAN-G was achieved by selecting stable transfected cell clones. Genomic integration and expression we re verified by Southern and Northern blotting and electrophoretic mobi lity shift assays. Growth was determined by cell number and xenografts transplanted into nude mice. Differentiation was examined by immunohi stochemistry. Results: Overexpression of RAR beta in DAN-G cells inhib ited cellular proliferation in vitro and in vivo. Furthermore, RAR bet a overexpression resulted in induction of cellular differentiation in xenografted tumors as evidenced by increased tumor cell expression of duct cell differentiation markers carcinoembryonic antigen (CEA), CA19 -9, and cytokeratin 7. Conclusions: Decreased expression of RAR beta p lays a key role in the maintenance of a malignant phenotype in human p ancreatic adenocarcinoma and therefore represents a novel target for e xperimental strategies in the treatment of pancreatic cancer patients.