title: Retinoic acid receptor gamma1 expression determines retinoid sensitivity in pancreatic carcinoma cells.
abstract: OBJECTIVE
  Retinoids inhibit growth and induce differentiation in a variety of pancreatic carcinoma cells. The goal of this study was to examine the molecular mechanisms responsible for retinoid sensitivity.
  
  
  METHODS
  Anchorage-independent growth was examined in AR42J, DSL-6A/C1, and Capan-2 cells using a human tumor clonogenic assay. Retinoid receptors were characterized by a reverse-transcription polymerase chain reaction. Retinoic acid receptor gamma1 (RARgamma1) was stably transfected into AR42J cells using lipofectamin and into DSL-6A/C1 using ballistomagnetic gene transfer. Receptor expression was verified using Southern and Northern blotting as well as electrophoretic mobility shift 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 RARgamma1 expression was observed in both retinoid-resistant cell lines, whereas all other retinoid receptor subtypes showed an identical expression pattern. Retinoid treatment of three independent RARgamma1-expressing cell clones of AR42J and DSL-6A/C1 cells resulted in pronounced growth inhibition compared with wild-type control cells.
  
  
  CONCLUSIONS
  RARgamma1 expression determines sensitivity of pancreatic carcinoma cells to retinoid-mediated growth inhibition and might therefore serve as a valuable predictive marker for retinoid treatment of pancreatic cancer.
authors.affiliation: Department of Gastroenterology, Klinikum Benjamin Franklin, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kaiser
authors.forename: M
authors.initials: M
authors.lastname: Wolf-Breitinger
authors.forename: A
authors.initials: A
authors.lastname: Albers
authors.forename: T
authors.initials: T
authors.lastname: Dorbic
authors.forename: B
authors.initials: B
authors.lastname: Wittig
authors.forename: E O
authors.initials: EO
authors.lastname: Riecken
authors.forename: S
authors.initials: S
authors.lastname: Rosewicz
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006801:Humans; D010179:Pancreas / Q000166:cytology / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D000097768:Retinoic Acid Receptor gamma
chemical_list: D000970:Antineoplastic Agents; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma