title: Different response to retinoic acid of two teratocarcinoma cell lines.
abstract: Retinoic acid (RA), a well-known inducer of differentiation, has been shown to regulate its own receptor gene expression in F9 teratocarcinoma cells. The homologous regulation of receptors by RA might be critical for RA-induced F9 cell differentiation. F9 cell lines from two different laboratories, named F9-1 and F9-2, were compared for retinoic acid receptor (RAR) and retinoid x receptor (RXR) gene expression in response to RA. The data show that both F9-1 and F9-2 cell lines are embryonal carcinoma cells, but of different phenotypes and different sensitivity to RA. In F9-1 cells, RA regulates all three RARs (alpha, beta, and gamma), two RXRs (alpha and gamma), two activin receptors (ActR II and IIB), and tissue-specific plasminogen activator (t-PA) gene expression. In F9-2 cells RA regulates only the RAR beta, RXR alpha, and t-PA genes. The induction of mRNA levels was much higher in F9-1 than in F9-2 cells. Different basal RAR gamma and RXR gamma mRNA levels were also noted. In these two cell lines F9-2 cells expressed greater amounts of RAR gamma 1, gamma 2, and gamma 3 mRNA isoforms, but lacked RXR gamma mRNA compared with F9-1 cells. Since RAR gamma 1 has been shown to exert an antagonistic effect on other types of RA receptors, the decreased sensitivity of F9-2 cells to RA might be due to its high level of RAR gamma 1 and/or low level of RXR gamma. This notion was in part supported by gel shift assay which demonstrated constitutive binding of RAR gamma to a RA responsive element (RAR beta E) in F9-2 cells. Further, the binding of nuclear protein to RAR beta E was increased upon RA treatment in F9-1 cells, but not in F9-2 cells. These differences in the regulation of RA receptors might determine the sensitivity of the two substrains of F9 cells to RA.
authors.affiliation: Department of Pathology, Harbor-UCLA Medical Center, Torrance 90509, USA.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Wan
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: T C
authors.initials: TC
authors.lastname: Wu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D007633:Keratins / Q000096:biosynthesis; D016256:Lewis X Antigen / Q000096:biosynthesis; D051379:Mice; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D047488:Retinoid X Receptors; D018243:Teratocarcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D016256:Lewis X Antigen; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin; D007633:Keratins