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Reduced phosphorylated ATM expression is associated with poor prognosis and gemcitabine resistance in pancreatic cancer

ABSTRACT: Reduced phosphorylated ATM expression is associated with poor prognosis and gemcitabine resistance in pancreatic cancer

PROVIDER: PRJNA932847 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23375260.fastq.gz	Fastqsanger.gz
	SRR23375261.fastq.gz	Fastqsanger.gz
	SRR23375262.fastq.gz	Fastqsanger.gz
	SRR23375263.fastq.gz	Fastqsanger.gz
	SRR23375264.fastq.gz	Fastqsanger.gz

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Reduced phosphorylated ATM expression is associated with poor prognosis and gemcitabine resistance in pancreatic cancer

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is associated with accumulation of particular oncogenic mutations and recent genetic sequencing studies have identified ataxia telangiectasia-mutated (ATM) mutations in PDAC cohorts. Here we report that conditional deletion of ATM in a mouse model of PDAC induces a greater number of proliferative precursor lesions coupled with a pronounced fibrotic reaction. ATM-targeted mice display altered TGFβ-superfamily signalling and enhanced epithelial-to-mesenchymal transition (EMT) coupled with shortened survival. Notably, our mouse model recapitulates many features of more aggressive human PDAC subtypes. Particularly, we report that low expression of ATM predicts EMT, a gene signature specific for Bmp4 signalling and poor prognosis in human PDAC. Our data suggest an intimate link between ATM expression and pancreatic cancer progression in mice and men. KC (Atm+/+) and AKC (Atm-/-) mouse pancreata at 5 weeks old (n= 3 KC; n= 3 AKC) or 10 weeks old (n=3 KC; n=4 AKC) were subjected to microarray analysis.

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