A. Kaiser et al., RETINOIC ACID RECEPTOR GAMMA(1) EXPRESSION DETERMINES RETINOID SENSITIVITY IN PANCREATIC-CARCINOMA CELLS, Gastroenterology, 115(4), 1998, pp. 967-977
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.