Immunohistochemistry (IHC) was utilized to assess the CD105 expression in tumor tissue, and real-time quantitative PCR (qPCR) was used to determine the mRNA expression of CD105 of monocytes in tumor tissue and PB, as well as the mRNA expression of TGFβ1, Smad1-4 in tumor tissue.
AA treatment increased the expression of SMAD1, a tumor suppressor gene known to be suppressed by methylation, and increased chemosensitivity of lymphoma cells.
Indeed, Smad1 is identified as a dominant downstream effector of Uev1A, which unravels the mechanism underlying Uev1A-orchestrated tumor suppression in OS.
Smad1/5/4 triple knockout mice were sterile and had significantly increased survival and delayed tumor development compared to those for the Smad1/5 double knockout mice.
TGF-β signaling is modulated by the coreceptor Endoglin (Eng), which shows a tumor suppressor activity in epithelial cells and regulates the ALK1-Smad1,5,8 as well as the ALK5-Smad2,3 signaling pathways.
Quantitative analysis of BMP signaling revealed ambivalent results: decreased tumor cell expression of the BMP response gene Id-1 but increased staining for phospho-SMAD 1,5, 8.