Retinoic acid-induced transition from protein kinase C beta to protein kinase C alpha in differentiated F9 cells: correlation with altered regulation of proto-oncogene expression by phorbol esters.
Retinoic acid (RA) induced differentiation of F9 embryonal carcinoma cells is accompanied by changes in cellular responsiveness to extracellular signals. These changes include an increase in the AP1 transcription factor that is associated with the expression of differentiation markers (e.g., cytokeratin 18 and plasminogen activator). Since AP1 activity is a target for protein kinase C (PKC)-regulated changes in gene expression, we have examined the effects of RA on the expression and function of the PKC isozymes. F9 stem cells express PKC beta, delta, epsilon, and zeta. RA-induced differentiation to primitive endoderm led to a transition from PKC beta to PKC alpha expression. Additional treatment with dibutyryl cyclic AMP (dbcAMP), required for terminal differentiation into parietal endoderm, further increased PKC alpha expression and total PKC activity. RA and dbcAMP had negligible effects on the expression of PKC delta, epsilon, and zeta. The PKC beta to PKC alpha transition was specific for parietal endoderm; aggregation of RA-treated F9 cells induced visceral endoderm differentiation with elevated expression of PKC beta. The PKC activation with phorbol esters induced the expression of c-fos, c-jun, and junB proto-oncogenes in F9 stem cells. In the presence of either RA or RA and dbcAMP, phorbol ester treatment enhanced the expression of type IV collagen, a parietal endoderm marker. It also increased the expression of c-jun gene but not c-fos. The specific involvement of PKC beta in c-fos induction and PKC alpha in type IV collagen induction was confirmed in each PKC isozyme-transfected F9 cells. Together, our data demonstrate that the RA-induced (and dbcAMP-induced) changes in conventional PKC expression alters gene expression during parietal endoderm formation.[1]References
- Retinoic acid-induced transition from protein kinase C beta to protein kinase C alpha in differentiated F9 cells: correlation with altered regulation of proto-oncogene expression by phorbol esters. Khuri, F.R., Cho, Y., Talmage, D.A. Cell Growth Differ. (1996) [Pubmed]
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