Increased expression of glycolysis-associated genes in oncogene-transformed and growth-accelerated states.

An accelerated rate of glucose transport and catabolism is a common characteristic of cellular transformation. We have previously found elevated expression of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in human pancreatic and colonic adenocarcinomas (Schek et al.: Cancer Res 48:6354-6359, 1988). To investigate further the expression of this enzyme in the process of tumorigenesis, we examined GAPDH expression in a panel of oncogene-transformed fibroblasts. Significant elevations of GAPDH mRNA and glucose transporter protein mRNA levels were observed in ras- and mos-transformed NIH 3T3 cells, whereas little or no change was found in c-src-, v-src-, c-myc-, E1A-, v-fos-, and PKC-gamma-transfected cells. Furthermore, the level of GAPDH mRNA correlated with the transformed state in a series of ras-transformed and revertant cell lines. Immunoblot analysis confirmed that GAPDH polypeptide was significantly elevated in the cell lines with elevated mRNA levels. Cell cycle analysis data suggested that the effect on GAPDH expression correlated with oncogene expression rather than cell growth fraction. These results suggest that altered GAPDH gene expression occurs during some growth deregulated states, and this, along with increased glucose transporter (and possibly other glycolytic enzyme) expression, is likely to contribute to the increased metabolic capacity of cells in these states.