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. 2021 Sep 2;297(4):101162. doi: 10.1016/j.jbc.2021.101162

Figure 6.

Figure 6

TGF-β/activin signaling is upregulated and necessary for maintaining CDK7i resistance.A, Gene Set Enrichment Analysis showing the enrichment of the TGF-β family signaling gene signature (79) in MDA-MB-468R and MDA-MB-231R cells compared with their respective sensitive/parental cells. B, changes in the expression of activin A mRNA (INHBA) was confirmed in MDA-MB-468 and MDA-MB-231 cells. C, western blot analysis of INHBA protein expression in resistant compared with sensitive/parental MDA-MB-468 cells. The larger-molecular-weight protein band for INHBA is the glycosylated isoform. D, protein expression of the intrinsic inhibitor of activin, follistatin (FST) was reduced in resistant compared with sensitive/parental MDA-MB-468 and MDA-MB-231 cells. E, phosphorylation of SMAD3 is induced in resistant compared with sensitive/parental cells. F, western blot analysis of total SMAD3 expression in MDA-MB-468 and MDA-MB-231-sensitive/parental and resistant cells. G, resistant and sensitive/parental cells were treated with 11.2 μM SB431542 for MDA-MB-468 or 5.6 μM SB431542 for MDA-MB-231 or vehicle for 48 h prior to generating 72-h THZ1 dose–response curves. The THZ1 dose–response curves are significantly different when cotreated with the SB compound compared with vehicle in the resistant cells according to a sum-of-squares F test with a p-value <0.05. These data are the results of three independent experiments. Bars are means ± SD. Protein expression is quantified relative to the total protein. ∗p < 0.05.