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PMID: 9823968 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Retinoic acid receptor alpha mediates growth inhibition by retinoids in rat pancreatic carcinoma DSL-6A/C1 cells.

British journal of cancer ·Vol. 78 ·No. 10 ·1998-11-00 ·Pages 1288-95

Brembeck FH, Kaiser A, Detjen K, Hotz H, Foitzik T, Buhr HJ, Riecken EO, Rosewicz S

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.

MeSH Terms
Animals Carcinoma, Ductal, Breast/metabolism,pathology Cell Division/drug effects Cell Transformation, Neoplastic Pancreatic Neoplasms/metabolism,pathology Rats Receptors, Retinoic Acid/biosynthesis,physiology Retinoids/pharmacology Tumor Cells, Cultured
Chemicals
Receptors, Retinoic Acid Retinoids
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Brembeck F H
Department of Gastroenterology, Medizinische Klinik I, Klinikum Benjamin Franklin, FU Berlin/Germany.
Kaiser A
Detjen K
Hotz H
Foitzik T
Buhr H J
Riecken E O
Rosewicz S
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
DOI
10.1038/bjc.1998.673
Published
1998-11-00
Pages
1288-95
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2063193
Subset
IM
External Links
PubMed source DOI: 10.1038/bjc.1998.673 PMC Full Text View journal details
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