Retinoic acid-induced differentiation of a nontumorigenic embryonal carcinoma cell mutant created through retroviral insertion.
A mutant embryonal carcinoma cell line, NR1-6, was created through retroviral insertion. We have previously reported that due to a single insertional event the mutant cell line is altered in regard to both its morphology and its tumorigenic capacity. We now report that this same cell line is also aberrant in its differentiative potential following exposure to the morphogen retinoic acid (RA). Unlike the parental NR1-0 cells, the NR1-6 cells apparently do not respond to RA by elaborating primitive endodermal derivatives in monolayer culture but rather appear morphologically to differentiate into mesodermal cells. This hypothesis is substantiated by the observation that RA treatment induces the transcription of both Endo A and B mRNA in parental but not mutant cells. No differences have been observed in the transcription of other RA sensitive markers such as c-myc, tissue plasminogen activator, collagen type IV, and laminin. In addition, the mutant cells are quantitatively much more sensitive to RA induction than are the parental cells, achieving full differentiation within 72 h of treatment with 10(-10) M RA. The parental cells, in contrast, will only differentiate at concentrations of 10(-5) or 10(-6) M RA, following 5 to 7 days of treatment. A spontaneous revertant cell line, which was isolated from an NR1-6 population and lacks the retroviral insert, is identical to the parental population in all parameters. Therefore, these data indicate that, in this case at least, a single genetic locus is involved in regulating both the qualitative and quantitative response of EC cells to RA-induced differentiation, as well as their morphology and tumorigenic potential.
Dietrich
J
J
Department of Biological Sciences, SUNY Albany 12222.
Shin
H S
HS
McCormick
P J
PJ
D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005814:Genes, Viral; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016254:Mutagenesis, Insertional; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012190:Retroviridae / Q000235:genetics*; D013724:Teratoma / Q000235:genetics* / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000473:pathology
D007797:Laminin; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014212:Tretinoin; D003094:Collagen; D010959:Tissue Plasminogen Activator