Retinoic acid receptor beta regulates growth and differentiation in human pancreatic carcinoma cells

Background & Aims: Retinoic acid receptor beta (RAR beta) expression is lost or decreased during malignant transformation in human pancreatic adenocarcinoma. The aim of this study was to evaluate the role of RAR beta expression in the propagation of a malignant phenotype in human pancreatic carcinoma cells. Methods: Overexpression of RAR beta in the human pancreatic carcinoma cell line DAN-G was achieved by selecting stable transfected cell clones. Genomic integration and expression were verified by Southern and Northern blotting and electrophoretic mobility shift assays. Growth was determined by cell number and xenografts transplanted into nude mice. Differentiation was examined by immunohistochemistry. Results: Overexpression of RAR beta in DAN-G cells inhibited cellular proliferation in vitro and in vivo. Furthermore, RAR beta 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 plays a key role in the maintenance of a malignant phenotype in human pancreatic adenocarcinoma and therefore represents a novel target for experimental strategies in the treatment of pancreatic cancer patients.