Studies on the tumor promoting mechanism of hard and soft segment models of polyetherurethane: Tyr265 phosphorylation of connexin43 is a key step in the GJIC inhibitory reaction induced by polyetherurethane.

Gap junctional intercellular communication (GJIC) is inhibited by 4,4'-di(ethoxycarboamide) diphenylmethane (MDU) and polytetramethylene oxide 1000 (PTMO1000), which are model chemicals of hard and soft segments of polyetherurethane (PEU), respectively. In our previous study, we suggested that the inhibition of GJIC induced by MDU and PTMO1000 may lead to accelerate promotion step by both segments after the initiation step by hard segment, MDU. To examine this hypothesis, we established connexin 43 overexpressed clones from Balb/c 3T3 A31-1-1 clones (A31-1-1 cells) by transfection. Here we show that these clones acquired much higher GJIC ability than parental A31-1-1 cells and kept them even if MDU or PTMO1000 was added to the culture. We also found that Mutation of Cx43 at Tyr-265 resulted in reduced inhibition of GJIC induced by MDU and PTMO1000. These findings suggest that inhibition of GJIC by PEU may be caused by Tyr-265 phosphorylation of Cx43 molecule.