Functional PKC in vivo analysis using deficient mouse models.

The aim of our group is to identify PKC (protein kinase C) in vivo function by analysing individual PKC knockouts we have generated over the past few years. The general approach we are using to identify target tissues and/or defined cell populations within the mouse for further investigation is a detailed expression analysis of individual PKC isoforms. For these purposes, we have established several specific tools in the past that allow us to follow up isoform-specific PKC expression on a very precise level. Doing so, we have started to investigate PKC expression profiles under various tumour conditions in mice. As predicted, we were able to identify various PKC isoforms to be either up- or down-regulated during the development and progression of certain tumours, implying that these isoforms are substantially linked to the biology of these tumours. In order to prove this hypothesis, we then crossed relevant PKC knockout lines on the appropriate tumour background and analysed tumour growth and progression under PKC-deficient conditions. Exemplary of this approach, recent data generated with PKCalpha-deficient APC(Min) (adenomatous polyposis coli) mice identify PKCalpha in this system acting as a tumour suppressor instead of being a promoter as suggested from PMA data.