RETINOIC ACID RECEPTOR GAMMA(1) EXPRESSION DETERMINES RETINOID SENSITIVITY IN PANCREATIC-CARCINOMA CELLS

Background & Aims: Retinoids inhibit growth and induce differentiation in a variety of pancreatic carcinoma cells. The goal of this study wa s to examine the molecular mechanisms responsible for retinoid sensiti vity. Methods: Anchorage-independent growth was examined in AR42J, DSL -6A/C1, and Capan-2 cells using a human tumor clonogenic assay. Retino id receptors were characterized by a reverse-transcription polymerase chain reaction. Retinoic acid receptor yl (RAR gamma(1)) was stably tr ansfected into AR42J cells using lipofectamin and into DSL-6A/C1 using ballistomagnetic gene transfer. Receptor expression was verified usin g Southern and Northern blotting as well as electrophoretic mobility s hift assays. Results: Retinoid treatment resulted in a dose-dependent growth inhibition of Capan-2 cells, whereas growth was not affected in AR42J and DSL-6A/C1 cells. A selective loss of RAR gamma(1) expressio n was observed in both retinoid-resistant cell lines, whereas all othe r retinoid receptor subtypes showed an identical expression pattern. R etinoid treatment of three independent RAR gamma(1)-expressing cell cl ones of AR42J and DSL-6A/C1 cells resulted in pronounced growth inhibi tion compared with wild-type control cells. Conclusions: RAR gamma(1) expression determines sensitivity of pancreatic carcinoma cells to ret inoid-mediated growth inhibition and might therefore serve as a valuab le predictive marker for retinoid treatment of pancreatic cancer.