Regulation of Egr-1 (Zfp-6) and c-fos expression in differentiating embryonal carcinoma cells.
The Egr-1 gene (zfp-6) encodes a 'zinc finger'-type transcription factor that is one of the early growth response genes induced, together with c-fos proto-oncogene, in many cell types. Our earlier work indicated that Egr-1 and c-fos may also play roles in differentiation and we now present data to show some features of their regulation. Transcriptional regulation accounts at least partly for the increased steady-state levels of Egr-1 mRNA in differentiating teratocarcinoma cells; this rate increases threefold over the 7-10 days of differentiation of P19 embryonal carcinoma cells with both 0.5% DMSO (to give predominantly cardiac muscle) and 1 microM retinoic acid (to give nerve and glial cells). The stability of Egr-1 transcripts remains the same (T1/2 = 90 min) in undifferentiated EC and differentiated cell products. In contrast, transcripts for c-fos are barely detectable in EC cells and increase 20-fold during differentiation. The basis for this is a marked increase in stability of c-fos mRNA after differentiation. The protein products of both genes parallel the steady-state levels of their mRNAs, but both proteins become more stable in differentiated cells. This is particularly marked for c-Fos protein, which appears as a distinct 58 kDa species in terminally differentiated P19 cells. Both Egr-1 and c-Fos proteins remain at high constitutive levels in differentiated cells indicating a distinct role for these transcription factors, For instance, it appears that this form of Fos protein may not repress the synthesis of the Egr-1 gene as it does during transient expression of serum-stimulated genes.
Darland
T
T
La Jolla Cancer Research Foundation, California 92037.
Samuels
M
M
Edwards
S A
SA
Sukhatme
V P
VP
Adamson
E D
ED
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000473:pathology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013724:Teratoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014158:Transcription, Genetic / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics*
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D014212:Tretinoin; D004121:Dimethyl Sulfoxide