REGULATION OF GLUCOSE-TRANSPORT BY INTERLEUKIN-3 IN GROWTH FACTOR-DEPENDENT AND ONCOGENE-TRANSFORMED BONE-MARROW-DERIVED CELL-LINES

Growth factors maintain cell viability and promote cell growth by stim ulating glucose transport into cells and by progressing cells through the cell cycle. In the short term, effects on glucose transport involv e transporter activation, while in the longer term increased gene expr ession is involved. This study aimed to investigate growth factor regu lation of glucose transport in an interleukin (IL)-3-dependent bone ma rrow-derived cell line and its oncogene-transformed counterparts. 32D clone 3 (32Dcl3) cells and cells transfected with temperature-sensitiv e (ts) res and abl oncogenes, were treated with and without IL-3 and t heir ability to take up 2-deoxy-D-glucose compared. Transformed cells, which are not dependent on IL-3 for growth at the permissive temperat ure of 32 degrees C, exhibited a two-to six-fold higher proliferative response, enhanced tyrosine kinase activity and c-myc expression than control cells optimally stimulated with IL-3. Compared with control 32 Dcl3 cells, P-deoxy-D-glucose uptake was also 36-76% higher in transfo rmed cells. The increased glucose uptake in transformed cells was cons istent with 2.5-fold higher affinity of the glucose transporters for g lucose. IL-3 stimulated glucose uptake in both control and oncogene-tr ansformed cells. With control and res-transformed cells, enhanced gluc ose uptake in response to IL-3 was associated with increased affinity of glucose transporters for glucose but with abl-transformed cells, no significant affinity changes were observed. IL-3 also increased gluco se transporter expression in both control and oncogene-transformed cel ls, suggesting that increased transporter expression as well as change s in transporter affinity for glucose can affect glucose uptake. (C) 1 997 Elsevier Science Ltd.