Overexpression of protein kinase Cβ1 restores mitogenic responses of enterocytic differentiated colon carcinoma cells to diacylglycerol and basic FGF

초록

Previous studies have shown that the HD3 human enterocytic differentiated colon carcinoma cell lines having low PKCβ activity did not respond to diacylglycerol and basic FGF by growth and by activation of pp57 MAP kinase, but undifferentiated cell lines exhibiting high PKCβ activity did. To confirm a role of PKCβ in colonocyte mitogenesis, derivatives of HD3 cell line that stably overexpress a full-length of cDNA encoding the β<inf>1</inf> isoform of human PKC were generated. The abundance and activity of PKCβ in two of the these cell lines, PKC3 and PKC8 were much higher than those in the C1 control cell line that carries the vector lacking the PKCβ<inf>1</inf> cDNA insert. Following exposure to diacylglycerol or basic FGF, proliferation of PKC3 and PKC8 cells increased about 50%: but this effect was not seen with the control C1 cells. Also, in contrast to the control cells, the PKCβ<inf>1</inf>-overproducing cells displayed activation of pp57 MAP kinase when treated with diacylglycerol and basic FGF as undifferentiated cell lines did. These results provide direct evidence that PKCβ<inf>1</inf> which plays a key role in mitogenic responses of colon carcinoma cells to diacylglycerol and basic FGF is down-regulated in enterocytic differentiation of colon cells.

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