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Up-regulation of p21 WAF1 expression in myeloid cells is activated by the protein kinase C pathway
Journal article   Peer reviewed

Up-regulation of p21 WAF1 expression in myeloid cells is activated by the protein kinase C pathway

J Schwaller, U.R Peters, Th Pabst, G Niklaus, D.E Macfarlane, M.F Fey and A Tobler
British journal of cancer, Vol.76(12), pp.1554-1557
12/1997
DOI: 10.1038/bjc.1997.595
PMID: 9413940

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Abstract

Phorbol-12-myristate-13-acetate (PMA) induces p21WAF-1 expression in human myeloid leukaemic HL-60 cells. We show that this induction is specifically mediated by protein kinase C (PKC). In addition, the PKC inhibitor Ro 31-8220 with predominant PKC-alpha isoform specificity almost completely inhibited PMA-induced up-regulation of p21WAF1 in HL-60 cells as well as in the myelomonocytic leukaemic U937 cells. Pretreatment of HL-60 cells with Ro 31-8220 also inhibited PMA-induced activation of c-raf-1, a known PKC alpha target. In the phorbol ester-tolerant HL-60 subline (PET) with PKC-beta isoform deficiency PMA or bryostatin-1 induced p21WAF1 expression, but to a lesser extent than in wild-type HL-60 cells. In PET cells, Ro 31-8220 also inhibited PMA and bryostatin-1-induced up-regulation of p21WAF1 expression. Our findings indicate that at least in HL-60 cells up-regulation of p21WAF-1 is specifically activated by PKC. We suggest that PKC isoforms other than beta, presumably the PKC-alpha isoform, are involved in this process.

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