Retinoic acid receptor gamma1 expression determines retinoid sensitivity in pancreatic carcinoma cells.
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.
Kaiser
A
A
Department of Gastroenterology, Klinikum Benjamin Franklin, Berlin, Germany.
Wolf-Breitinger
M
M
Albers
A
A
Dorbic
T
T
Wittig
B
B
Riecken
E O
EO
Rosewicz
S
S
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
D000970:Antineoplastic Agents; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma