Protein kinase Cdelta-mediated signal to ornithine decarboxylase induction is independent of skin tumor suppression.
Protein Kinase Cdelta (PKCdelta), a Ca(2+)-independent, phospholipid-dependent serine/threonine kinase, is among the PKC isoforms expressed in mouse epidermis. We reported that FVB/N transgenic mice that overexpress ( approximately eightfold) PKCdelta protein in basal epidermal cells are resistant to skin tumor formation by the 7,12-dimethylbenz(a)anthracene (DMBA)-initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promotion protocol. However, despite being resistant to skin tumor promotion by TPA, PKCdelta transgenic mice elicited a 3-4-fold increase in TPA-induced epidermal ODC activity and putrescine levels than their wild-type littermates. PKCdelta was observed to be the key component of the TPA signal transduction pathways to the induction of mouse epidermal ODC activity. To determine if TPA-induced ODC activity and associated putrescine levels in PKCdelta transgenic mice contributed to PKCdelta-mediated suppression of skin tumor promotion by TPA, the irreversible inhibitor of ODC, alpha-difluoromethylornithine (DFMO), was used. PKCdelta transgenic mice and their wild-type littermates were initiated with 100 nmol DMBA and then promoted twice weekly with 5 nmol TPA. The experimental group was given 0.5% DFMO in their drinking water, while the control group was given tap water. After 25 weeks, the number of papillomas (>2 mm) per mouse was counted. The DFMO treatment did not affect the skin tumor multiplicity of PKCdelta transgenic mice. These results indicate that PKCdelta- induced ODC activity is not involved in PKCdelta-mediated tumor suppression. Thus, the signaling pathways via PKCdelta to epidermal ODC induction and skin tumor suppression appear to be independent.[1]References
- Protein kinase Cdelta-mediated signal to ornithine decarboxylase induction is independent of skin tumor suppression. Wheeler, D.L., Reddig, P.J., Dreckschmidt, N.E., Leitges, M., Verma, A.K. Oncogene (2002) [Pubmed]
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