Faculty Collaboration Database

Retinoic acid induction of major histocompatibility complex class I genes in NTera-2 embryonal carcinoma cells involves induction of NF-kappa B (p50-p65) and retinoic acid receptor beta-retinoid X receptor beta heterodimers. Mol Cell Biol 1993 Oct;13(10):6157-69

Date

10/01/1993

Pubmed ID

8413217

Pubmed Central ID

PMC364675

DOI

10.1128/mcb.13.10.6157-6169.1993

Scopus ID

2-s2.0-0027452408 (requires institutional sign-in at Scopus site)   70 Citations

Abstract

Retinoic acid (RA) treatment of human embryonal carcinoma (EC) NTera-2 (NT2) cells induces expression of major histocompatibility complex (MHC) class I and beta-2 microglobulin surface molecules. We found that this induction was accompanied by increased levels of MHC class I mRNA, which was attributable to the activation of the two conserved upstream enhancers, region I (NF-kappa B like) and region II. This activation coincided with the induction of nuclear factor binding activities specific for the two enhancers. Region I binding activity was not present in undifferentiated NT2 cells, but binding of an NF-kappa B heterodimer, p50-p65, was induced following RA treatment. The p50-p65 heterodimer was produced as a result of de novo induction of p50 and p65 mRNAs. Region II binding activity was present in undifferentiated cells at low levels but was greatly augmented by RA treatment because of activation of a nuclear hormone receptor heterodimer composed of the retinoid X receptor (RXR beta) and the RA receptor (RAR beta). The RXR beta-RAR beta heterodimer also bound RA responsive elements present in other genes which are likely to be involved in RA triggering of EC cell differentiation. Furthermore, transfection of p50 and p65 into undifferentiated NT2 cells synergistically activated region I-dependent MHC class I reporter activity. A similar increase in MHC class I reporter activity was demonstrated by cotransfection of RXR beta and RAR beta. These data show that following RA treatment, heterodimers of two transcription factor families are induced to bind to the MHC enhancers, which at least partly accounts for RA induction of MHC class I expression in NT2 EC cells.

Author List

Segars JH, Nagata T, Bours V, Medin JA, Franzoso G, Blanco JC, Drew PD, Becker KG, An J, Tang T

Author

Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Cell Line
DNA
Embryonal Carcinoma Stem Cells
Gene Expression Regulation
Genes, MHC Class I
Humans
Mice
Molecular Sequence Data
NF-kappa B
Neoplastic Stem Cells
Promoter Regions, Genetic
Receptors, Cytoplasmic and Nuclear
Receptors, Retinoic Acid
Retinoid X Receptors
Transcription Factors
Transfection
Tretinoin