Abstract
In McA-RH 8994 rat hepatoma cells, all-trans-retinoic acid (t-RA) induces expression of the α-fetoprotein (AFP) and albumin genes and results in a phenotype similar to differentiated fetal hepatocytes. The present study elucidated the mechanism involved in AFP gene regulation mediated by retinoic acid. Northern blot analyses demonstrated that 9-cis-retinoic acid (c-RA), a ligand for retinoid x receptors (RXRs), also induced expression of the AFP gene in McA-RH 8994 cells. The induction was time- and dose-dependent. Northern blots and transfection assays using the 7.3 kb full-length regulatory region of the AFP gene demonstrated that c-RA was more effective than t-RA in regulating expression of the AFP gene. At 10-7 M, c-RA increased AFP mRNA 5-fold and chloramphenicol acetyltransferase (CAT) activity 2.5-fold. In contrast, t-RA at a concentration of 10-7 M exerted no significant effect; 10-6 to 10-5 M t-RA was needed to affect AFP gene expression. These data suggested that activation of RXRs is essential for the regulation of the AFP gene. Co-transfection experiments revealed that overexpression of RXRα in McA-RH 8994 cells further enhanced the CAT activity induced by c-RA. In addition, c-RA didnot alter the half-life of AFP mRNA. Thus, RXRα may play a crucial role in transcriptional regulation of the AFP gene and in controlling hepatocyte phenotype.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 101-108 |
| Number of pages | 8 |
| Journal | Journal of Molecular Endocrinology |
| Volume | 14 |
| Issue number | 1 |
| State | Published - 1995 |
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ASJC Scopus subject areas
- Endocrinology
Cite this
9-cis-retinoic acid is more effective than all-trans-retinoic acid in upregulating expression of the α-fetoprotein gene. / Wan, Yu-Jui Yvonne; Pan, T.; Wang, L.; Locker, J.; Wu, T. C J.
In: Journal of Molecular Endocrinology, Vol. 14, No. 1, 1995, p. 101-108.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 9-cis-retinoic acid is more effective than all-trans-retinoic acid in upregulating expression of the α-fetoprotein gene
AU - Wan, Yu-Jui Yvonne
AU - Pan, T.
AU - Wang, L.
AU - Locker, J.
AU - Wu, T. C J
PY - 1995
Y1 - 1995
N2 - In McA-RH 8994 rat hepatoma cells, all-trans-retinoic acid (t-RA) induces expression of the α-fetoprotein (AFP) and albumin genes and results in a phenotype similar to differentiated fetal hepatocytes. The present study elucidated the mechanism involved in AFP gene regulation mediated by retinoic acid. Northern blot analyses demonstrated that 9-cis-retinoic acid (c-RA), a ligand for retinoid x receptors (RXRs), also induced expression of the AFP gene in McA-RH 8994 cells. The induction was time- and dose-dependent. Northern blots and transfection assays using the 7.3 kb full-length regulatory region of the AFP gene demonstrated that c-RA was more effective than t-RA in regulating expression of the AFP gene. At 10-7 M, c-RA increased AFP mRNA 5-fold and chloramphenicol acetyltransferase (CAT) activity 2.5-fold. In contrast, t-RA at a concentration of 10-7 M exerted no significant effect; 10-6 to 10-5 M t-RA was needed to affect AFP gene expression. These data suggested that activation of RXRs is essential for the regulation of the AFP gene. Co-transfection experiments revealed that overexpression of RXRα in McA-RH 8994 cells further enhanced the CAT activity induced by c-RA. In addition, c-RA didnot alter the half-life of AFP mRNA. Thus, RXRα may play a crucial role in transcriptional regulation of the AFP gene and in controlling hepatocyte phenotype.
AB - In McA-RH 8994 rat hepatoma cells, all-trans-retinoic acid (t-RA) induces expression of the α-fetoprotein (AFP) and albumin genes and results in a phenotype similar to differentiated fetal hepatocytes. The present study elucidated the mechanism involved in AFP gene regulation mediated by retinoic acid. Northern blot analyses demonstrated that 9-cis-retinoic acid (c-RA), a ligand for retinoid x receptors (RXRs), also induced expression of the AFP gene in McA-RH 8994 cells. The induction was time- and dose-dependent. Northern blots and transfection assays using the 7.3 kb full-length regulatory region of the AFP gene demonstrated that c-RA was more effective than t-RA in regulating expression of the AFP gene. At 10-7 M, c-RA increased AFP mRNA 5-fold and chloramphenicol acetyltransferase (CAT) activity 2.5-fold. In contrast, t-RA at a concentration of 10-7 M exerted no significant effect; 10-6 to 10-5 M t-RA was needed to affect AFP gene expression. These data suggested that activation of RXRs is essential for the regulation of the AFP gene. Co-transfection experiments revealed that overexpression of RXRα in McA-RH 8994 cells further enhanced the CAT activity induced by c-RA. In addition, c-RA didnot alter the half-life of AFP mRNA. Thus, RXRα may play a crucial role in transcriptional regulation of the AFP gene and in controlling hepatocyte phenotype.
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UR - http://www.scopus.com/inward/citedby.url?scp=0028960119&partnerID=8YFLogxK
M3 - Article
C2 - 7539613
AN - SCOPUS:0028960119
VL - 14
SP - 101
EP - 108
JO - Journal of Molecular Endocrinology
JF - Journal of Molecular Endocrinology
SN - 0952-5041
IS - 1
ER -