[Study on the relationship between two second-messenger pathways on the regulation of proliferation and...

By using an inducer of differentiation (HMBA) and blockers of signal pathways, the relationship between two second-messenger pathways (DG-PKC, cAMP-PKA) in inducer-mediated MGc80-3 cell differentiation was studied. Cells were treated with HMBA for 24 h, levels of DG decreased by 64.7%, activity of PKC decreased by 28.7%, while levels of cAMP and rate of it's protein binding increased by 62% and 32.6% respectively (after treated for 48 h, the result was more remarkable). PKA-R II distributed in nuclei. H7 (PKC inhibitor) was used to substitute for HMBA to block the DG-PKC pathway. After treatment for 24 h, the levels of DG and activity of PCK both decreased, while the levels of cAMP increased 1.04 times. On the contrary, PKA inhibitor was added while HMBA was used to induce cell differentiation, cAMP-PKA pathway was blocked, levels of cAMP and rate of it's protein binding decreased. But levels of DG and activity of PKC both increased to the levels of control cells. At this time, PKA-R II distributed only in cytoplasm. These results suggest that harmonious relations of the positive and negative regulation of cAMP-PKA and DG-PKC systems in cells during the proliferation and differentiation of cells. It also showed that positive regulation of PI system may play a leading role in MGc80-3 cells. It let to normal regulation of two signal pathway out of control to remain malignant phenotype of these cells.