PKC Isoenzyme expression and cellular responses to phorbol ester in JEG-3 choriocarcinoma cells

Protein kinase C (PKC) is a key regulatory enzyme involved in the transduction of extracellular growth signals to the cell nucleus. It occurs in several isoforms, the exact functional roles of which have not been established as yet. The tumor-promoting agent 12-O-tetradecanoyl-phorbol acetate (TPA) is the classic activator of PKC and modulates the activity of the activating protein-1 (AP-1) transcription factor complex via this pathway. AP-1, in turn, induces cell proliferation in many tissues. In the present study, the PKC isoenzyme expression pattern in JEG-3 choriocarcinoma cells was analyzed. The results were compared with those obtained in HEC-1B endometrium adenocarcinoma cells, which had previously been characterized in this respect. To gain insight into the possible functional consequences of different PKC expression patterns, cell proliferation rates and AP-1 activity in response to TPA in both cell lines was studied. Western blot analysis of the PKC isoenzyme expression pattern revealed that JEG-3 cells are deficient in the PKC α, δ, and ε isoforms. These isoenzymes are strongly expressed in HEC-1B cells, with the α and δ being constitutively active. As opposed to HEC-1B cells, JEG-3 cells did not show an enhanced proliferation rate in response to TPA. Furthermore, TPA-treated JEG-3 cells did not exhibit any change in cell shape and refractility as observed in HEC-1B cells. AP-1 activity, as determined by a transfected AP-1 luciferase reporter plasmid, was induced 10-fold by TPA in JEG-3 cells, yet only threefold in HEC-1B cells. It is concluded from these data that differential expression of a subset of PKCs, e.g., the α, δ, and ε isoforms, may serve as an indicator of the proliferative potential in response to growth factors and mitogens. Furthermore, our data indicate that the inducibility of AP-1 activity does not necessarily reflect the proliferative capacity of a given cell type in response to classical tumor promoters such as phorbol ester.