Protein kinase C α modulates growth and differentiation in Caco-2 cells

Abstract

Background & Aims: Caco-2 cells have been used extensively to elucidate events involved in intestinal cell proliferation and differentiation. Because individual isoforms of protein kinase C (PKC) and p21 waf1, a cyclin-dependent kinase inhibitor, may regulate these processes, their role(s) on the growth and differentiation of Caco-2 cells were assessed. Methods: Protein abundance and subcellular distribution of several PKC isoforms, as well as the expression of p21 waf1, were examined in preconfluent and postconfluent cells. Results: In cells at confluence (~7 days postplating) and during their postconfluent phase (up to 20 days postplating), both total protein expression of PKC-α and its particulate distribution increased compared with their 3-day postplated counterparts. These findings were in agreement with those obtained by immunocytochemistry of PKC-α. In contrast, neither the total expression nor the subcellular distribution of PKC-βI, -βII, -δ, or -ζ changed significantly during these time periods. In addition, the expression of p21 waf1, which can be induced by PKC-α, increased in postconfluent cells. Conclusions: PKC-α, but not other isoforms of PKC, may modulate the proliferation and differentiation of Caco-2 cells. This regulation appears to be mediated, at least in part, via a mechanism involving p21 waf1. GASTROENTEROLOGY 1998;114:503-509