Fig. 7: NeoGATA3 interferes with the PR-dependent growth arrest.

a Graph showing the relative percentage of BrdU+ cells in the indicated cell population after 24 h treatment with vehicle or 100 nM P4. b Graph showing the relative cell viability measured with crystal violet staining of the indicated cell populations after vehicle-treatment, 6 days treatment with 100 nM P4, or 3 days with 100 nM P4 followed by additional 3 days in normal medium. Cells were kept in normal medium containing hormones. In a, b the results are normalized to the respective vehicle control and are shown as mean ± standard deviation of at least three independent experiments. Two-sided Student’s t test *P < 0.05. c Western blot showing expression of PR, wtGATA3, and neoGATA3 in T47D cells transduced with the indicated constructs and treated with progesterone (P4) (100 nM) for 24 h in normal medium. GAPDH was used as loading control. d The working model: neoGATA3 is a weak oncogenic driver with highly context-dependent functions. In a progesterone-rich environment, it interferes with the antiproliferative PR-driven program, whereas in an estrogen-rich context it blunts the pro-mitogenic ER-dependent response. Progesterone drops faster than estrogen at menopause, therefore it is possible that neoGATA3 mutations are enriched in premenopause patients because of this context-dependent opposite effects.