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PMID: 2162058 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Retinoic acid, dibutyryl-cAMP, and differentiation affect the expression of retinoic acid receptors in F9 cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 12 ·1990-06-00 ·Pages 4804-8

Martin CA, Ziegler LM, Napoli JL

Abstract

Expression of the retinoic acid receptors alpha and beta (RAR-alpha and RAR-beta) was examined in F9 cells, an embryonal carcinoma cell model established for the study of retinoid metabolism and function. Addition of retinoic acid to F9 cell medium caused a dose-dependent increase in RAR-beta mRNA within 3 hr that reached 5- to 30-fold greater than the constitutively expressed mRNA by 24 hr. The elevation in mRNA resulted from increased transcription, as demonstrated by nuclear run-on transcription, did not require protein synthesis, and required the constant presence of retinoic acid. N6,O2'-Dibutyryl-cAMP attenuated the retinoic acid-induced increase in RAR-beta mRNA by a post-transcriptional mechanism. In contrast, RAR-alpha mRNA in F9 stem cells was affected less (1.2- to 1.4-fold increase) by retinoic acid and decreased 3-fold transiently when fresh serum was added to the medium. Differentiation of F9 cells resulted in increased steady-state levels of RAR-beta mRNA in primitive (4-fold), parietal (3-fold), and visceral (8-fold) endoderm but decreased steady-state levels of RAR-alpha mRNA in primitive (2-fold), parietal (3-fold), and visceral (1.4-fold) endoderm. These data demonstrate that RAR-beta is a primary target gene for retinoic acid in a characterized model of retinoid function, indicate that constitutive expression of both RAR-beta and RAR-alpha is dependent upon the differentiation state, and suggest hormonal modulation of RAR-beta by cAMP and modulation of RAR-alpha by serum factors. These results distinguish the effects of serum, cAMP, and retinoic acid on the expression of RAR from the effects mediated by differentiation.

MeSH Terms
Animals Bucladesine/pharmacology Carrier Proteins/genetics Cell Differentiation Cell Line Cell Nucleus/metabolism DNA Probes Gene Expression/drug effects Kinetics Nucleic Acid Hybridization RNA, Messenger/drug effects,genetics Receptors, Retinoic Acid Restriction Mapping Teratoma Transcription, Genetic/drug effects Tretinoin/pharmacology
Chemicals
Carrier Proteins DNA Probes RNA, Messenger Receptors, Retinoic Acid Tretinoin Bucladesine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Martin C A
Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214.
Ziegler L M
Napoli J L
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.12.4804
Published
1990-06-00
Pages
4804-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC54206
Subset
IM
Grants
NIDDK NIH HHS · DK36870 · United States
External Links
PubMed source DOI: 10.1073/pnas.87.12.4804 PMC Full Text View journal details
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