Abstract |
Treatment of F9 teratocarcinoma stem cells with retinoic acid (RA) causes their irreversible differentiation into extraembryonic endoderm. To elucidate the role of the cellular retinoic acid binding protein-I ( CRABP-I) in this differentiation process, we have generated several different stably transfected F9 stem cell lines expressing either elevated or reduced levels of functional CRABP-I protein. Stably transfected lines expressing elevated levels of CRABP-I exhibit an 80-90% reduction in the RA induced expression of retinoic acid receptor ( RAR) beta, laminin B1, and collagen type IV (alpha 1) mRNAs at low exogenous RA concentrations, but this reduction is eliminated at higher RA concentrations. Thus, greater expression of CRABP-I reduces the potency of RA in this differentiation system. Moreover, transfection of a CRABP-I expression vector into F9 cells resulted in five- and threefold decreases in the activation of the laminin B1 RARE ( retinoic acid response element) and the RAR beta RARE, respectively, as measured from RARE/CAT expression vectors in transient transfection assays. These results support the idea that CRABP-I sequesters RA within the cell and thereby prevents RA from acting to regulate differentiation specific gene expression. Our data suggest a mechanism whereby the level of CRABP-I can regulate responsiveness to RA during development.
|
Authors | J F Boylan, L J Gudas |
Journal | The Journal of cell biology
(J Cell Biol)
Vol. 112
Issue 5
Pg. 965-79
(Mar 1991)
ISSN: 0021-9525 [Print] United States |
PMID | 1847931
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Carrier Proteins
- DNA, Antisense
- Laminin
- Receptors, Retinoic Acid
- Tretinoin
- Collagen
- DNA
|
Topics |
- Animals
- Blotting, Southern
- Carrier Proteins
(genetics, metabolism)
- Cell Differentiation
(genetics)
- Collagen
(genetics)
- DNA
(metabolism)
- DNA, Antisense
(metabolism)
- Embryonal Carcinoma Stem Cells
- Gene Expression Regulation
- Laminin
(genetics)
- Mice
- Neoplastic Stem Cells
- Receptors, Retinoic Acid
- Transfection
- Tretinoin
(pharmacology)
- Tumor Cells, Cultured
|