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- W2754802215 abstract "e23088 Background: Programmed death ligand 1 (PD-L1, CD274) is currently being investigated as a therapeutic target in breast cancer (BC), however its transcriptional regulation has not been elucidated. Methods: Three BC cells lines, one negative (MCF7) and two positive (MDA-MB-231, BT549) for PD-L1 were used. Protein expression of potential regulators of PD-L1, including Myc, STAT3, p-rpS6 (mTOR effector), Erk and p53 was assessed by western blotting and immunohistochemistry. Furthermore, transfections with small interfering RNAs (siRNAs) of selected proteins or plasmids and pharmacologic inhibition were performed. Fluorescent in situ hybridization (FISH) analysis was used for PD-L1 gene amplification studies. Publically available gene expression data derived from The Cancer Genome Atlas (TCGA) database (cBioportal) were analyzed for correlations between mRNA levels of PD-L1 and potential regulators. Results: PD-L1 gene amplification was not detected in BC cells expressing PD-L1, suggesting non-genetic regulation of PD-L1 expression. Additionally, the correlation between CD274 transcript levels and copy-number alterations (CNA) in primary BC was weak. Pharmacological treatment with either Myc (expressed in MDA-MB-231) or mTOR (p-rpS6 expressed in all three cell lines) inhibitors did not affect PD-L1 expression. STAT3 protein was expressed in all cell lines and STAT3 mRNA levels had a weak positive correlation with PD-L1 (Spearman’s rho = 0.25) in the TCGA dataset. Both gene silencing using STAT3 siRNA and pharmacologic inhibition of STAT3 activity resulted in decreased PD-L1 protein levels in BT549 and MDA-MB-231 cells respectively. Multiple DNA binding sites for STAT3 were identified in silico on the PD-L1 gene promoter suggesting that the observed regulatory effects are likely transcriptional. Conclusions: STAT3 can act as an inducer of PD-L1 expression, while Myc and mTOR seem to have no effect in PD-L1 regulation in BC." @default.
- W2754802215 created "2017-09-25" @default.
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- W2754802215 date "2017-05-20" @default.
- W2754802215 modified "2023-10-02" @default.
- W2754802215 title "Regulation of PD-L1 in breast cancer." @default.
- W2754802215 doi "https://doi.org/10.1200/jco.2017.35.15_suppl.e23088" @default.
- W2754802215 hasPublicationYear "2017" @default.
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