Differential induction of 12-O-tetradecanoylphorbol-13-acetate sequence gene expression in murine melanocytes and melanoma cells

✍ Scribed by Gavin Brooks; Martin W. Goss; Ian R. Hart

• Book ID: 102946485
• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 528 KB
• Volume: 5
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.2940050414

✦ Synopsis

Abstract

We previously showed that growth of the nontumorigenic, immortal murine melanocyte line Mel‐ab correlates with the depletion of protein kinase C (PKC), whereas quiescence is associated with elevated levels of this enzyme (Brooks G, et al., Cancer Res 51: 3281–3288, 1991). Here we report responses that occur in these cells downstream of PKC activation or downregulation. We examined induction of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐inducible sequence (TIS) gene expression in Mel‐ab melanocytes and in their transformed counterparts, B16 melanoma cells. Exposure of quiescent Mel‐ab cells to the PKC‐activating phorbol esters TPA or sapintoxin A at 81 nM for 2 h increased levels of mRNA for six of seven TIS genes examined (twofold to 80‐fold increase in steady‐state RNA levels for TIS 1, 7, 8, 11, 21, and 28 (c‐fos); TIS 10 expression was not affected). No induction of 115 gene expression was observed either in growing Mel‐ab cells maintained in 324 nM phorbol 12,13‐dibutyrate or in B16 cells previously unexposed to phorbol esters, in which normal PKC levels were endogenously depressed. The cAMP‐elevating agents choleratoxin (10 nM) and dibutyryl cyclic AMP (2.5 mM) increased levels of TIS mRNA (with the exception of TIS 10) in both proliferating Mel‐ab and B16 cells, suggesting that downregulation of the PKC pathway is specific and not a consequence of a general inhibition of all signalling pathways. © 1992 Wiley‐List. Inc.