Glutamine Synthetase Is a Genetic Determinant of Cell Type–Specific Glutamine Independence in Breast Epithelia
Figure 4
Contribution of luminal expression of GLUL and GATA3 to the glutamine-independence phenotype.
(A) The normalized cell survival of breast cancer cell lines (luminal-type: blue, basal-type: green) with or without treatment with GS inhibitor, L-MS, in the absence of glutamine. (B) The degree of cellular survival under glutamine deprivation for MCF7 (luminal cell) treated with either control or two siRNAs targeting GLUL. (C) The degree of cellular survival under glutamine deprivation for MDAMB231 (basal cell) transfected with either control vector or GLUL overexpression construct. (D) The changes of GLUL, GLS and GLS2 in the mouse mammary epithelia cells transfected with GATA3 from array analysis derived from an independent study [38]. (E) The levels of GLUL in MCF7 cells treated with either control or siRNA targeting GATA3. (F) The levels of GLUL in the MDAMB231 cells transfected with either control vectors or GATA3 expression constructs. (G) The relative survival under glutamine deprivation of MCF7 cells treated with control or two independent siRNAs targeting GATA3. (H) The cell survival rates shown in MDAMB231 cells with overexpression of control vector or GATA3 under glutamine deprivation. (I) The promoter regions of the GLUL with two potential binding sites of GATA3 are shown. (The sequences underlined indicate primer locations.) (J) The enrichment of different promoter regions of GLUL, ER (positive control) and albumin (negative control) which have been immunoprecipitated with GATA3 and control IgG antibodies. (All statistical comparisons: *p<0.05, **p<0.01)