Cloning of several genes coding for retinoic acid nuclear receptors in the mouse embryonal carcinoma cell line PCC7-MZ1.
Mouse embryonal carcinoma cell line PCC7-Mz1 can be induced by retinoic acid (RA) to differentiate into several well defined phenotypes of neuroectodermal origin (Lang, E. et al. (1989) J. Cell. Biol. 109, 2481-2493). Several subclones of the cell line (clonal variants) differ from each other in their developmental potential. To test whether these differences in cellular fate are due to somatic mutations in specific genes of these cells, we have cloned full length cDNAs coding for the alpha 1 and beta 2 isoforms, and partial length cDNAs coding for the alpha 2, beta 1 and beta 3 isoforms of the retinoic acid nuclear receptor (RAR). The cloned cDNAs did not differ in sequence from those of normal mouse cells. Using as probe the beta 2-RAR promoter region from mouse liver, we also checked for restriction fragment length polymorphism in the promoter regions of RA-inducible and RA-resistant cell variants. No alterations in this region of RAR genes was found in the clonal variants tested. The different patterns of derivatives produced by the variants upon exposure to RA therefore cannot be caused by somatic mutations in RAR genes of the tumor cell lines.
Laboratory of Molecular Neurobiology, Johannes Gutenberg University School of Medicine, Mainz, Germany.
R
R
Heiermann
M
M
Rentrop
E
E
Lang
A
A
Maelicke
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D054278:Embryonal Carcinoma Stem Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D014212:Tretinoin; D004247:DNA