Transcriptional regulation of retinoic acid receptor beta in retinoic acid-sensitive and -resistant P19 embryocarcinoma cells
| Autor: | Fae Kruyt, Frank A.E. Kruyt, Ce Vandenbrink, Mj Donath, Lhk Defize, W. Kruijer, Pierre Chambon, Pt Vandersaag, Philippe Kastner |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Embryology
Embryonal Carcinoma Stem Cells Transcription Genetic Receptors Retinoic Acid Molecular Sequence Data Retinoic acid Drug Resistance Retinoic acid receptor beta Tretinoin Biology Transfection chemistry.chemical_compound Mice Transcriptional regulation Tumor Cells Cultured Animals RNA Neoplasm Promoter Regions Genetic Gene Base Sequence Molecular biology Neoplasm Proteins Gene Expression Regulation Neoplastic Retinoic acid receptor Nuclear receptor chemistry Cell culture embryonic structures Neoplastic Stem Cells Chromosome Deletion Carrier Proteins Developmental Biology |
| Zdroj: | Mechanisms of development. 33(3) |
| ISSN: | 0925-4773 |
| Popis: | As in other embryocarcinoma (EC) cell lines retinoic acid (RA) rapidly induces expression of the nuclear retinoic acid receptor (RAR) beta in murine P19 EC cells, while RAR alpha is expressed constitutively. In the RA-resistant P19 EC-derived RAC65 cells, however, there is no such induction and an aberrant (smaller) RAR alpha transcript is expressed. RAR gamma 1 is expressed at low levels in both cell lines. To study the regulation of the RAR beta gene and the possible involvement of RAR alpha protein in transcriptional activation of the RAR beta gene we transfected these cells with a construct containing a 1.6 kb promoter fragment of the human RAR beta gene fused to the CAT gene. Upon transient assays in P19 EC cells CAT activity is enhanced rapidly by RA, to more than 100-fold in a concentration-dependent fashion. On the contrary no activity can be observed in the RA-resistant RAC65 cells; however, co-transfection of hRAR alpha, hRAR beta or hRAR gamma 1 restores the RA-dependent induction of CAT activity. These results clearly show that RAR alpha and RAR gamma 1 can transactivate the RAR beta gene; that RAR beta can stimulate its own expression and that resistance to RA in RAC65 cells is probably due to the altered RAR alpha transcript present in these cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|