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PMID: 8105479 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Loss of retinoic acid receptor gamma function in F9 cells by gene disruption results in aberrant Hoxa-1 expression and differentiation upon retinoic acid treatment.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 20 ·1993-10-15 ·Pages 9601-5

Boylan JF, Lohnes D, Taneja R, Chambon P, Gudas LJ

Abstract

Retinoic acid (RA) signal transduction is believed to be mediated through several high-affinity nuclear receptors [RA receptors (RARs) and retinoid X receptors], which are members of the steroid/thyroid/vitamin D superfamily and function as transcription factors. Why multiple RARs exist and what gene targets are regulated by each of the three receptors remain compelling questions in developmental biology. Through targeted disruption of both RAR gamma alleles, we have identified several differentiation-specific genes that are regulated either directly or indirectly by RAR gamma in F9 embryonal carcinoma cells. These include genes encoding Hoxa-1 (Hox-1.6) and the extracellular matrix proteins laminin B1 and collagen type IV (alpha 1), all of which are RA inducible in wild-type F9 embryonal carcinoma cells but are not significantly induced in the RAR gamma-/- lines. In contrast, transcripts encoding Hoxb-1 (Hox-2.9) and cellular RA binding protein II (CRABPII) are activated by RA for a longer period of time in the RAR gamma-/- lines compared to the wild-type F9 line. Not all RA-responsive genes are aberrantly expressed; Rex-1, RAR beta, and SPARC transcripts are regulated in the RAR gamma-/- lines as they are in F9 wild-type cells. Our results support the idea that each RAR may regulate different subsets of RA-responsive genes, which may explain, in part, the complex regulation of developmental processes by retinoids.

Related Genes
CRABP-II Hoxa-1 Hoxb-1 RAR&bgr RARYagr Rex SPARC
MeSH Terms
Animals Carcinoma, Embryonal/pathology Cell Differentiation/drug effects Gene Expression Regulation Genes, Homeobox In Vitro Techniques Mice Mutagenesis, Insertional RNA, Messenger/genetics Receptors, Retinoic Acid/physiology Tretinoin/pharmacology Tumor Cells, Cultured
Chemicals
RNA, Messenger Receptors, Retinoic Acid Tretinoin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Boylan J F
Department of Pharmacology, Cornell University Medical College, New York, NY 10021.
Lohnes D
Taneja R
Chambon P
Gudas L J
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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.90.20.9601
Published
1993-10-15
Pages
9601-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC47617
Subset
IM
Grants
NCI NIH HHS · 1F32 CA09251-01 · United States
NCI NIH HHS · R01CA43796 · United States
NICHD NIH HHS · R0IHD24319 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.20.9601 PMC Full Text View journal details
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