Antisense glutaminase inhibition modifies the O-GlcNAc pattern and flux through the hexosamine pathway in breast cancer cells

DONADIO AC, LOBO C, TOSINA M, DE LA ROSA V, MARTÍN-RUFIÁN M, CAMPOS-SANDOVAL JA, MATÉS JM, MARQUEZ J, ALONSO FJ, SEGURA JA

Liss

Lugar: United States; Año: 2008 vol. 103 p. 800 - 800

font face="TimesNewRomanPSMT"> Glutamine behaves as a key nutrient for tumours and rapidly dividing cells. Glutaminase is the main glutamine-utilizing enzyme in these cells, and its activity correlates well with glutamine consumption and growth rate. We have carried out the antisense L-type glutaminase inhibition in human MCF7 breast cancer cells in order to study its effect on the hexosamine pathway and the pattern of protein Oglycosylation. The antisense mRNA glutaminase expressing cells, named ORF19, presented a 50% lower proliferation rate than parental cells and showed a more differentiated phenotype. ORF19 cells had an 80 % reduction in glutamine:fructose-6- P amidotransferase activity, the rate-limiting step of hexosamine pathway. Hexosamine pathway provides UDP-GlcNAc, neces