Changes in mRNAs for enzymes of glutamine metabolism in the tumor-bearing mouse

Changes in the relative mRNA levels of phosphate-activated glutaminase (PAG ) and glutamine synthetase (GS) in the liver and kidney of mice bearing a h ighly malignant strain of Ehrlich ascites tumor cells were determined at di fferent days after tumor transplantation. Kidney glutaminase mRNA steadily increased, reaching maximum values at day 10 of tumor growth, while those o f glutamine synthetase did not change, resulting in a sustained decrease of the GS/PAG ratio in the kidneys of tumor-bearing animals compared with con trols. However; the GS/PAG ratio in the liver significantly increase, mainl y due to a strong decrease in PAG, whereas GS mRNA levels remained almost u naffected. These results, combined with those previously reported on enzyma tic activities and glutamine concentrations in the host-tumor system, sugge st a long-term regulation of the host glutaminase enzymes in order to incre ase the circulating glutamine levels needed for tumor growth.