Retinoic acid receptor α mediates growth inhibition by retinoids in rat pancreatic carcinoma DSL-6A/C1 cells (original) (raw)

British Journal of Cancer volume 78, pages 1288–1295 (1998)Cite this article

Abstract

During carcinogenesis, pancreatic acinar cells can dedifferentiate into ductal adenocarcinoma of the pancreas. DSL-6A/C1 cells represent an in vitro model of this carcinogenic sequence. This study was designed to examine the effects of retinoids on cell growth in DSL-6A/C1 cells and to characterize further the molecular mechanisms underlying the antiproliferative actions of retinoids. Treatment of DSL-6A/C1 cells with retinoids results in a time- and dose-dependent inhibition of cell growth, paralleled by a retinoid-mediated transactivation of a pTK::betaRAREx2-luciferase reporter construct transiently transfected into DSL-6A/C1 cells. Retinoid receptor expression was evaluated by reverse transcriptase polymerase chain reaction (RT-PCR) using subtype-specific primers and demonstrated expression of retinoic acid receptor alpha (RAR-alpha), RAR-beta and retinoid X receptor alpha (RXR-alpha). Using a panel of receptor subtype-specific agonists, the RAR-alpha specific agonist Ro 40-6055 was the most potent retinoid in terms of growth inhibition. Furthermore, all-trans-retinoic acid-mediated growth inhibition and transactivation was completely blocked by the RAR-alpha-specific antagonist Ro 41-5253. In summary, the RAR-alpha subtype predominantly mediates the antiproliferative effects of retinoids in DSL-6A/C1 cells. Furthermore, this cell system provides a feasible tool to study the molecular mechanisms underlying the growth inhibitory effects of retinoids in ductal pancreatic carcinoma cells derived from a primary acinar cell phenotype.

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Authors and Affiliations

  1. Department of Gastroenterology, Medizinische Klinik I, Klinikum Benjamin Franklin, Berlin, FU, Germany
    FH Brembeck

Authors

  1. FH Brembeck
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  2. A Kaiser
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  3. K Detjen
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  4. H Hotz
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  5. T Foitzik
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  6. HJ Buhr
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  7. E-O Riecken
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  8. S Rosewicz
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Brembeck, F., Kaiser, A., Detjen, K. et al. Retinoic acid receptor α mediates growth inhibition by retinoids in rat pancreatic carcinoma DSL-6A/C1 cells.Br J Cancer 78, 1288–1295 (1998). https://doi.org/10.1038/bjc.1998.673

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