33 research outputs found
DNA binding-dependent androgen receptor signaling contributes to gender differences and has physiological actions in males and females
We used our genomic androgen receptor (AR) knockout (ARKO) mouse model, in which the AR is unable to bind DNA to: 1) document gender differences between males and females; 2) identify the genomic (DNA-binding-dependent) AR-mediated actions in males; 3) determine the contribution of genomic AR-mediated actions to these gender differences; and 4) identify physiological genomic AR-mediated actions in females. At 9 weeks of age, control males had higher body, heart and kidney mass, lower spleen mass, and longer and larger bones compared to control females. Compared to control males, ARKO males had lower body and kidney mass, higher splenic mass, and reductions in cortical and trabecular bone. Deletion of the AR in ARKO males abolished the gender differences in heart and cortical bone. Compared with control females, ARKO females had normal body weight, but 14% lower heart mass and heart weight/ body weight ratio. Relative kidney mass was also reduced, and relative spleen mass was increased. ARKO females had a significant reduction in cortical bone growth and changes in trabecular architecture, although with no net change in trabecular bone volume. In conclusion, we have shown that androgens acting via the genomic AR signaling pathway mediate, at least in part, the gender differences in body mass, heart, kidney, spleen, and bone, and play a physiological role in the regulation of cardiac, kidney and splenic size, cortical bone growth, and trabecular bone architecture in females.
Supplementary Figure 2 from Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression
IPI-926 treatment alters cellular composition in the tumor microenvironment.</p
Supplementary Table 8 from Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression
Lymphoid network.Regulatory network for PDAC-associated lymphoid cells, listing the inferred transcriptional targets (Target) for each regulatory protein (Regulator). Association weight (AW) and association mode (AM) are scores to quantify strength/direction of interaction. Sign indicates directionality of the interaction (1 = transactivating, -1 = transrepressing).</p
Supplementary Table 9 from Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression
Myeloid network.Regulatory network for PDAC-associated myeloid cells, listing the inferred transcriptional targets (Target) for each regulatory protein (Regulator). Association weight (AW) and association mode (AM) are scores to quantify strength/direction of interaction. Sign indicates directionality of the interaction (1 = transactivating, -1 = transrepressing).</p
Supplementary Figure 7 from Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression
WNT Distribution and Expression of Downstream Targets.</p