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Published on: June 21, 2016
Retinoic acid receptor gamma1 expression determines retinoid sensitivity in pancreatic carcinoma cells
A Kaiser1, M Wolf-Breitinger, A Albers
1Department of Gastroenterology, Klinikum Benjamin Franklin, Berlin, Germany.
Background & Aims:
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.
Insights
Retinoic acid receptor gamma1 (RARgamma1) expression dictates pancreatic cancer cell response to retinoids. Restoring RARgamma1 in resistant cells re-sensitized them to retinoid-driven growth inhibition.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Retinoids are known to inhibit growth and induce differentiation in pancreatic carcinoma cells.
- Understanding the molecular basis of retinoid sensitivity is crucial for effective pancreatic cancer treatment.
Purpose of the Study:
- To investigate the molecular mechanisms underlying retinoid sensitivity in pancreatic cancer cells.
- To identify key factors determining cellular response to retinoid therapy.
Main Methods:
- Assessed anchorage-independent growth of pancreatic cancer cell lines (AR42J, DSL-6A/C1, Capan-2) using a human tumor clonogenic assay.
- Characterized retinoid receptor expression via reverse-transcription polymerase chain reaction.
- Stably transfected retinoic acid receptor gamma1 (RARgamma1) into retinoid-resistant cell lines and verified expression using molecular techniques.
Main Results:
- Capan-2 cells showed dose-dependent growth inhibition with retinoid treatment, while AR42J and DSL-6A/C1 cells were resistant.
- Retinoid-resistant cell lines exhibited a selective loss of RARgamma1 expression.
- Re-expression of RARgamma1 in AR42J and DSL-6A/C1 cells led to significant growth inhibition upon retinoid treatment.
Conclusions:
- RARgamma1 expression is a critical determinant of pancreatic carcinoma cell sensitivity to retinoid-induced growth inhibition.
- RARgamma1 may serve as a predictive biomarker for retinoid treatment efficacy in pancreatic cancer.
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