Hexose uptake as an indicator of JB6 mouse epidermal cell resistance to the mitogenic activity of TPA.

JB6 mouse epidermal cells have been selected for resistance to the tumor-promoting phorbol diester TPA for (1) the plateau density mitogenic (M) response, and (2) the promotion of tumor cell phenotype (P) response. The purpose of this study was to determine the relationship of hexose uptake to the two TPA-dependent processes. Monolayers of JB6 mouse epidermal cells showing one of four different phenotypes (M+P+, M+P-, M-P+, M-P-) were exposed to 60 nM [3H(G)]2-deoxy-D-glucose (2DG) with or without TPA (10 ng/ml) stimulation. The TPA mitogen-sensitive (M+P+/-) cells, when in logarithmic growth, had a lower basal 2DG uptake rate than TPA mitogen-resistant (M-P+/-) cells. At plateau density, however, only the M+P+ cells had a significantly lower basal rate. The M+ (TPA mitogen-sensitive) cells (with low basal rates), when preincubated with TPA, exhibited a two to threefold increase in 2DG uptake, while the M- (TPA mitogen-resistant) lines, which already showed elevated rates, remained unchanged. There was also a positive association between TPA mitogen sensitivity and slower growth rate. These results suggest that low hexose sugar uptake is related to TPA mitogen sensitivity, but not to promotion sensitivity. Hence the cell's ability to increase its uptake rate may be required for the cells to respond to mitogenic stimulation by TPA.