Mutant GATA3 Actively Promotes the Growth of Normal and Malignant Mammary Cells

NATASHA EMMANUEL; KRISTOPHER A. LOFGREN; ESTHER A. PETERSON; DAVID R. MEIER; ERIC H. JUNG; PARAIC A. KENNY

doi:10.21873/anticanres.12745

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Figure 1.
Mammary specific expression of GATA3^335fs in transgenic mice leads to precocious lobuloalveolar development. A. MMTV-GATA3^335fs construct with GATA3^335fs cloned downstream of the luminal cell-specific MMTV-LTR promoter. B. Expression of GATA3^335fs transgenic protein in virgin, pregnant, and lactating mouse mammary glands analyzed by western blot. MCF7 cells, which express this mutant, were used as a positive control. E-cadherin, an epithelial cell marker, was used as a loading control. C. Representative carmine-stained mammary gland whole mounts in metestrus-matched 9 week MMTV-GATA3^335fs and littermate wildtype controls. D. The extent of mammary gland development was quantified in 9 week old MMTV-GATA3^335fs (n=10) and wild-type (n=11) mice (p<0.0237, Fisher's Exact Test).
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Figure 2.
In vitro growth of ZR751 cells expressing ectopic mutant GATA3. 3D culture colony growth of the ZR751 stable cell lines in the absence or presence of 100 nM estradiol. The graph represents quantification of two independent experiments, each normalized to the median colony size in the control cultures at the time of quantification (**p<0.01, ***p<0.001 and ****p<0.0001, Mann-Whitney test). EV, ZR751 cells transfected with empty vector control; 308*, ZR751 cells expressing FLAG-tagged GATA3^308*; 335fs, ZR751 cells expressing FLAG-tagged GATA3^335fs.
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Figure 3.
In vivo growth of ZR751 cells expressing ectopic mutant GATA3. A. Kaplan–Meier curve showing the time to 100 mm³ xenograft tumor volume (*p<0.05, **p<0.01, Log-rank test). B. Comparison of growth rates of ZR751 xenograft tumors. Graph shows tumor volumes and standard error of the mean (n=20 per group, (*p<0.05, **p<0.01, ***p<0.001 and ****p<0.0001, Student's t-test). EV, ZR751 cells transfected with empty vector control; 308*, ZR751 cells expressing FLAG-tagged GATA3^308*; 335fs, ZR751 cells expressing FLAG-tagged GATA3^335fs.