In the light of the tests shown here where LY294002 causes ERa down-regulation equally in C4 HD and C4 HI tumors but tumor regression, by apoptosis and differentiation, only in C4 HI Dabrafenib price tumors, we postulate that AKT regulates C4 HI tumor growth, at the least partly, by maintaining ERa degrees. However, reduced levels of ERa are not adequate to cause tumor regression because inhibition of ERK1/2, which also reduced ERa levels, did not stop tumor growth. The finding of other mechanisms involved in tumor regression may help us to increase the effectiveness of tumor therapy to restrict tumor progression in this model. Two findings from our studies light emitting diode us to reconsider the commonly held opinion that as breast tumors progress from hormone dependent to hormone independent, they become less differentiated and more independent. The first observation suggests that C4 HI tumors are more differentiated and show more ductal like components than the original C4 HD tumors. This difference is not due to the existence of MPA within the C4 HD tumors because the administration of MPA to C4 HI tumors does not restrict its pattern of difference. We believe that in C4 Plastid HI tumors the PI3K/AKT and steroid receptor pathways converge in to a downstream sign that maintains the observed difference sample in C4 HI tumors. In support of the unity strategy, a) we’ve previously reported that C4 HI derived cancer associated fibroblasts can induce PR activation and cell proliferation of epithelial cells better than C4 HD derived cancer associated fibroblasts, t) we’ve previously established that blocking steroid receptors in vivo causes C4 HI tumor regression by differentiation and cell death, and C4 HD tumors deteriorate exclusively by cell death with no specific spatial pattern, and c) we show here that therapy with LY294002 in vivo causes tumor differentiation and regression only in C4 HI tumors. The 3D Matrigel process allowed us to localize apoptotic cells in and round the main lumen of C4 HI cell clusters treated with LY294002, a phenomenon that correlates with muscle differentiation. We are going to gauge the convergence theory further in future studies. The second observation implies that C4 HI tumors are more sensitive to PI3K/AKT and ERK regulation of ERa than C4 HD tumors, and they can maintain such regulation when they’re grown on Matrigel. In this culture system, we’ve found that C4 HI cells recover tissue polarity and lumen formation. In previous studies, we have demonstrated that SCg6 cells, a malignant mouse mammary cell line based on non malignant Scp2 cells, become unresponsive to basement membrane regulation of ERa expression. These data indicate that C4 HI cancers, while very metastatic in lymph supplier Celecoxib nodes and lungs are classified and are attentive to extra-cellular matrix signals. These findings claim that C4 HI tumors could be more painful and sensitive to the combination of hormonal, PI3K and integrin modulators to hinder their growth.