GATA1 Promotes Gemcitabine Resistance in Pancreatic Cancer through Antiapoptotic Pathway
Figure 7
Bcl-XL positively correlates with GATA1 and is a prognostic marker for PDAC. (a) Representative immunohistochemical staining of GATA1 and Bcl-XL in human PDAC tissues. Scale bar: 50 μm. (b) Correlation between GATA1 and Bcl-XL expression was analyzed in 172 PDAC samples (from Figure 1(d)) by Spearman rank correlation analysis. (c) Kaplan-Meier survival curves for overall survival and recurrence-free survival of 172 PDAC patients (from Figure 1(d)) according to the relative expression of Bcl-XL. (d) Kaplan-Meier survival curves of patients with (n=119) or without gemcitabine treatment (n = 53). (e) Graphic summary of GATA1 promoting gemcitabine resistance through antiapoptotic pathway. Gemcitabine causes apoptosis in mitochondrial pathway owing to DNA synthesis inhibition followed by DNA damage. GATA1 acts as a transcription activator by binding to the “GATG” site of Bcl-XL promoter region, leading to upregulation of Bcl-XL expression. Elevated Bcl-XL expression can counteract gemcitabine-induced apoptosis via binding to Bax, preventing the release of cytochrome c and thus preventing caspase activation.