Fig 2: Increased NE tumor incidence in 3PEKOT mice at 30 weeks of age. A. Three types of tumor lesions developed in TRAMP mice, including atypical hyperplasia (AH), neuroendocrine tumor (NE) and phyllodes (PHY). AH tumor cells express AR and SRC-3 but not Syp. NE tumor cells express Syp and SRC-3 but not AR. PHY tumor cells express AR but not Syp. The images of AH were taken from a tumor section of 3FloxT mouse, while the images of NE and PHY were taken from tumor sections of 3PEKOT mice. B. The frequency of each tumor type in the tumors of 24 and 30-week-old 3FloxT and 3PEKOT mice. See text for the results of statistical analysis.

Fig 3: SI-2 suppressed 4T1 breast cancer progression in BALB/cJ mice. A Western blot analysis of ERα, ERβ, PR, HER2, SRC-3, and β-Actin levels in E0771, 4T1, and MDA-MB-468 cells. B Determination of the IC50 values of SI-2 against E0771, 4T1, and MDA-MB-468 cells. C Luciferase activity imaging analysis of the growth of luciferase-labeled 4T1 breast tumors in BALB/cJ mice treated with vehicle and SI-2 (2.5 mg/kg). D Quantification of the luciferase activity of 4T1 breast tumors in Panel C. E 4T1 breast tumors harvested from tumor-bearing BALB/cJ mice treated with vehicle and SI-2 (2.5 mg/kg) on the 23rd day after drug treatment. F Quantification of the 4T1 tumor volume in Panel E. Tumor volume was calculated as 0.5 × length × width × width

Fig 4: Model for SI-2 and SRC-3 KD-mediated inhibition of breast tumor progression by the tumor-suppressing immune environment. SI-2 treatment and SRC-3 KD elevated Cxcl9 levels in breast tumors and then recruited Cxcr3-positive cytotoxic CD8+, CD4 + T cells, and NK cells into the tumor. The elevated numbers of cytotoxic immune cells elevate Ifng, leading to reduced breast cancer progression. Additionally, SI-2 treatment and SRC-3 KD promoted Il-1ra expression to suppress the proliferation of breast tumors. The graphic was generated by BioRender

Fig 5: The spatiotemporal expression patterns of SRC-1 and SRC-3 proteins during heart development. A. Western blot analysis of SRC-1 and SRC-3 in the hearts of E12.5, E14.5, E16.5, P0, P7, P14, P21 and P150 normal mice. Each tissue lysate was prepared from at least 3 mouse hearts. The α-tubulin served as a loading control. The arrow indicates a mouse IgG band detected by the secondary antibody. B. Detection of SRC-1 and SRC-3 positive cells by IHC in the E7.5, E8.5, E12.5, E14.5, P0, P7, P21 and P150 mouse hearts. The boxed areas in the first and third row panels are magnified in the second and fourth row panels, respectively. At least three mouse hearts at each stage were examined, and representative images were shown. hf, head fold; cv, common ventricular chamber of the primitive heart. C. Double immunofluorescent staining for SRC-1 and SRC-3 in the left ventricular wall of the E12.5 normal mouse heart. The nuclei were stained by DAPI. The boxed areas in the third and fifth panels are magnified in the fourth and sixth panels, respectively. The outlined area in the fourth panel indicates the heart chamber. The arrows indicate endothelial cells. The arrowheads indicate the epicardium. D. Double immunofluorescent staining for SRC-1 and MF20 and for SRC-3 and MF20 in the ventricular wall of the E12.5 normal mouse heart. Scale bars in panels B, C and D, 20 μm.