Cyclic AMP analogs and retinoic acid influence the expression of retinoic acid receptor alpha, beta, and gamma mRNAs in F9 teratocarcinoma cells

Retinoic acid (RA) receptor alpha (RAR alpha) and RAR gamma steady-state mRNA levels remained relatively constant over time after the addition of RA to F9 teratocarcinoma stem cells. In contrast, the steady-state RAR beta mRNA level started to increase within 12 h after the addition of RA and reached a 20-fold-higher level by 48 h. This RA-associated RAR beta mRNA increase was not prevented by protein synthesis inhibitors but was prevented by the addition of cyclic AMP analogs. In the presence of RA, cyclic AMP analogs also greatly reduced the RAR alpha and RAR gamma mRNA levels, even though cyclic AMP analogs alone did not alter these mRNA levels. The addition of either RA or RA plus cyclic AMP analogs did not result in changes in the three RAR mRNA half-lives. These results suggest that agents which elevate the internal cyclic AMP concentration may also affect the cellular response to RA by altering the expression of the RARs.

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c-myc regulation during retinoic acid-induced differentiation of F9 cells is posttranscriptional and associated with growth arrest

Molecular and Cellular Biology ◽

10.1128/mcb.6.2.518-524.1986 ◽

1986 ◽

Vol 6 (2) ◽

pp. 518-524

Author(s):

M Dean ◽

R A Levine ◽

J Campisi

Keyword(s):

Retinoic Acid ◽

Cyclic Amp ◽

Posttranscriptional Regulation ◽

Growth Arrest ◽

Mrna Levels ◽

F9 Cells ◽

Induction Of Differentiation ◽

Parietal Endoderm ◽

Arrest Growth ◽

F9 Teratocarcinoma

We have shown that c-myc mRNA levels decrease more than 20-fold when F9 teratocarcinoma stem cells are induced to arrest growth and terminally differentiate to parietal endoderm after exposure to retinoic acid and cyclic AMP (Campisi et al., Cell 36:241-247, 1984). Here, we demonstrate that although growth arrest and full expression of the differentiated phenotype required about 3 days, c-myc mRNA declined abruptly between 8 and 16 h after the addition of retinoic acid and cyclic AMP. The decline was independent of cyclic AMP. We found little or no change in the level of c-myc transcription during differentiation, although two other genes showed marked transcriptional regulation. Thus, decreased c-myc mRNA is a consequence of very early posttranscriptional regulation directed by retinoic acid. Differentiation was not fundamental to this regulation. We have shown that sodium butyrate blocks expression of the differentiated phenotype if added within 8 h of retinoic acid and cyclic AMP (Levine et al., Dev. Biol. 105:443-450, 1984). However, butyrate did not inhibit the decrease in c-myc mRNA. Furthermore, F9 cells partially arrested growth without differentiating when grown in isoleucine-deficient medium. Under these conditions, c-myc mRNA levels also declined. Our results suggest that induction of differentiation-specific genes may be under retinoic acid-mediated control dissimilar from that responsible for the decay of c-myc mRNA. In addition, they raise the possibility that growth arrest may be initiated by reduced c-myc expression.

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Retinoic acid-induced decrease of DNA synthesis and peroxidase mRNA levels in human thyroid cells expressing retinoic acid receptor alpha mRNA

Life Sciences ◽

10.1016/0024-3205(93)90256-3 ◽

1993 ◽

Vol 53 (13) ◽

pp. 1039-1048 ◽

Cited By ~ 8

Author(s):

L. del Senno ◽

R. Rossi ◽

D. Gandini ◽

R. Piva ◽

P. Franceschetti ◽

...

Keyword(s):

Retinoic Acid ◽

Dna Synthesis ◽

Retinoic Acid Receptor ◽

Human Thyroid ◽

Mrna Levels ◽

Retinoic Acid Receptor Alpha ◽

Thyroid Cells ◽

Acid Receptor ◽

Receptor Alpha

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E3, a hematopoietic-specific transcript directly regulated by the retinoic acid receptor alpha

Blood ◽

10.1182/blood.v88.7.2517.bloodjournal8872517 ◽

1996 ◽

Vol 88 (7) ◽

pp. 2517-2530 ◽

Cited By ~ 25

Author(s):

LM Scott ◽

L Mueller ◽

SJ Collins

Keyword(s):

Retinoic Acid ◽

Retinoic Acid Receptor ◽

Immediate Early ◽

Specific Gene ◽

Mrna Levels ◽

Retinoic Acid Receptor Alpha ◽

Granulocytic Differentiation ◽

Acid Receptor ◽

Receptor Alpha ◽

Alpha Gene

Retinoic acid (RA)-induced maturation mediated by the retinoic acid receptor alpha (RAR alpha) has been implicated in myeloid development. We have used differential hybridization analysis of a cDNA library constructed from the murine RA-inducible MPRO promyelocyte cell line to identify immediate-early genes induced by RA during granulocytic differentiation. E3, one of nine sequences identified, was upregulated in an immediate-early manner, with transcript levels peaking after 60 minutes exposure to RA. E3 transcripts were RA-inducible in HL60 cells, but not in an RA-resistant subclone, HL60R, that harbors a mutated RAR alpha gene. However, when HL60R cells were transduced with a functional copy of the RAR alpha gene, RA induced a 10-fold increase in E3 mRNA levels. E3 transcripts are present in the myeloid, B-lymphoid, and erythroid lineages, absent in nonhematopoietic cells, and encode a highly hydrophobic, potentially phosphorylated polypeptide of unknown function with significant homology to a putative protein expressed in myeloid cells. The murine E3 promoter harbors a single bipartite retinoic acid response element which in transient transfection assays conferred RA sensitivity. These results indicate that E3 is a hematopoietic-specific gene that is an immediate target for the activated RAR alpha during myelopoiesis.

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c-myc regulation during retinoic acid-induced differentiation of F9 cells is posttranscriptional and associated with growth arrest.

Molecular and Cellular Biology ◽

10.1128/mcb.6.2.518 ◽

1986 ◽

Vol 6 (2) ◽

pp. 518-524 ◽

Cited By ~ 91

Author(s):

M Dean ◽

R A Levine ◽

J Campisi

Keyword(s):

Retinoic Acid ◽

Cyclic Amp ◽

Posttranscriptional Regulation ◽

Growth Arrest ◽

Mrna Levels ◽

F9 Cells ◽

Induction Of Differentiation ◽

Parietal Endoderm ◽

Arrest Growth ◽

F9 Teratocarcinoma

We have shown that c-myc mRNA levels decrease more than 20-fold when F9 teratocarcinoma stem cells are induced to arrest growth and terminally differentiate to parietal endoderm after exposure to retinoic acid and cyclic AMP (Campisi et al., Cell 36:241-247, 1984). Here, we demonstrate that although growth arrest and full expression of the differentiated phenotype required about 3 days, c-myc mRNA declined abruptly between 8 and 16 h after the addition of retinoic acid and cyclic AMP. The decline was independent of cyclic AMP. We found little or no change in the level of c-myc transcription during differentiation, although two other genes showed marked transcriptional regulation. Thus, decreased c-myc mRNA is a consequence of very early posttranscriptional regulation directed by retinoic acid. Differentiation was not fundamental to this regulation. We have shown that sodium butyrate blocks expression of the differentiated phenotype if added within 8 h of retinoic acid and cyclic AMP (Levine et al., Dev. Biol. 105:443-450, 1984). However, butyrate did not inhibit the decrease in c-myc mRNA. Furthermore, F9 cells partially arrested growth without differentiating when grown in isoleucine-deficient medium. Under these conditions, c-myc mRNA levels also declined. Our results suggest that induction of differentiation-specific genes may be under retinoic acid-mediated control dissimilar from that responsible for the decay of c-myc mRNA. In addition, they raise the possibility that growth arrest may be initiated by reduced c-myc expression.

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Retinoid nutritional status differently affects the expression of Japanese quail retinoic acid receptor-beta isoform transcripts in a tissue-specific manner

Journal of Endocrinology ◽

10.1677/joe.0.1690281 ◽

2001 ◽

Vol 169 (2) ◽

pp. 281-290 ◽

Cited By ~ 3

Author(s):

ZW Fu ◽

T Kubo ◽

K Sugahara ◽

T Noguchi ◽

H Kato

Keyword(s):

Retinoic Acid ◽

Nutritional Status ◽

Japanese Quail ◽

Retinoic Acid Receptor ◽

Mrna Levels ◽

Tissue Specific ◽

Specific Manner ◽

Lower Magnitude ◽

Lung And Kidney ◽

Receptor Beta

We investigated the effects of vitamin A (VA) nutritional status on the levels of expression of retinoic acid (RA) receptor-beta (RARbeta) gene in the various tissues of Japanese quail. VA deficiency caused a significant decrease in the mRNA levels of brain, liver, heart, lung and kidney RARbeta2/beta4, whereas no change was observed in the level of testis RARbeta2 transcript. In contrast, reduction in the RARbeta1 transcript caused by VA depletion was observed only in the lung, remaining unchanged in the other tissues. The administration of RA to the VA-deficient quail rapidly induced the expression of RARbeta2/beta4 mRNAs in all the tissues examined, but RA increased the expression of RARbeta1 transcript in the liver, heart, lung and kidney at a lower magnitude. RA could not change the expression of the brain RARbeta1 transcript, while it induced the expression of the testis RARbeta1 mRNA in a temporal way. These results clearly indicate that VA nutritional status differently regulates the expression of RARbeta1 and RARbeta2/beta4 transcripts in a tissue-specific manner.

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