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EP300--a miRNA-regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas

Standard

EP300--a miRNA-regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas. / Mees, Soeren Torge; Mardin, Wolf Arif; Wendel, Claudia; Baeumer, Nicole; Willscher, Edith; Senninger, Norbert; Schleicher, Christina; Colombo-Benkmann, Mario; Haier, Joerg.

in: INT J CANCER, Jahrgang 126, Nr. 1, 01.01.2010, S. 114-24.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Mees, ST, Mardin, WA, Wendel, C, Baeumer, N, Willscher, E, Senninger, N, Schleicher, C, Colombo-Benkmann, M & Haier, J 2010, 'EP300--a miRNA-regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas', INT J CANCER, Jg. 126, Nr. 1, S. 114-24. https://doi.org/10.1002/ijc.24695

APA

Mees, S. T., Mardin, W. A., Wendel, C., Baeumer, N., Willscher, E., Senninger, N., Schleicher, C., Colombo-Benkmann, M., & Haier, J. (2010). EP300--a miRNA-regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas. INT J CANCER, 126(1), 114-24. https://doi.org/10.1002/ijc.24695

Vancouver

Mees ST, Mardin WA, Wendel C, Baeumer N, Willscher E, Senninger N et al. EP300--a miRNA-regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas. INT J CANCER. 2010 Jan 1;126(1):114-24. https://doi.org/10.1002/ijc.24695

Bibtex

@article{3a4ff41db0254f1690e0695b9749a4c1,
title = "EP300--a miRNA-regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas",
abstract = "Genetic and epigenetic alterations during development of pancreatic ductal adenocarcinomas (PDACs) are well known. This study investigates genetic and epigenetic data together with tumor biology to find specific alterations responsible for metastasis formation. Using 16 human PDAC cell lines in a murine orthotopic PDAC model, local infiltration and metastatic spread were assessed by standardized dissemination scores. The cell lines were further classified into 3 hierarchical groups according to their metastatic potential. Their mRNA and microRNA (miRNA) expression was profiled via mRNA-microarray as well as Taqman Low Density Array, and validated by single quantitative RT-PCR and Western blotting. In the highly metastatic group, a significant induction of EP300 targeting miRNAs miR-194 (fold change: 26.88), miR-200b (fold change: 61.65), miR-200c (fold change: 19.44) and miR-429 (fold change: 21.67) (p < 0.05) was detected. Corresponding to this, decreased expression of EP300 mRNA (p < 0.0001) and protein (p < 0.05) were detected in the highly metastatic PDAC cell lines with liver metastases compared to the nonmetastatic or marginally metastatic cell lines, while no correlation with local tumor growth was found. In conclusion, epigenetic alterations with upregulated EP300 targeting miRNAs miR-194, miR-200b, miR-200c and miR-429 are related to reduced EP300 mRNA and protein in PDAC. These results demonstrate that miRNAs might be able to modulate the expression of metastasis-specific suppressor genes and metastatic behavior in PDAC, suggesting diagnostic and therapeutic opportunities for EP300 and its targeting miRNAs in PDAC.",
keywords = "Animals, Blotting, Western, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, E1A-Associated p300 Protein, Gene Expression Profiling, Humans, Male, Mice, Mice, Nude, MicroRNAs, Neoplasm Metastasis, Oligonucleotide Array Sequence Analysis, Pancreatic Neoplasms, Reverse Transcriptase Polymerase Chain Reaction",
author = "Mees, {Soeren Torge} and Mardin, {Wolf Arif} and Claudia Wendel and Nicole Baeumer and Edith Willscher and Norbert Senninger and Christina Schleicher and Mario Colombo-Benkmann and Joerg Haier",
year = "2010",
month = jan,
day = "1",
doi = "10.1002/ijc.24695",
language = "English",
volume = "126",
pages = "114--24",
journal = "INT J CANCER",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "1",

}

RIS

TY - JOUR

T1 - EP300--a miRNA-regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas

AU - Mees, Soeren Torge

AU - Mardin, Wolf Arif

AU - Wendel, Claudia

AU - Baeumer, Nicole

AU - Willscher, Edith

AU - Senninger, Norbert

AU - Schleicher, Christina

AU - Colombo-Benkmann, Mario

AU - Haier, Joerg

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Genetic and epigenetic alterations during development of pancreatic ductal adenocarcinomas (PDACs) are well known. This study investigates genetic and epigenetic data together with tumor biology to find specific alterations responsible for metastasis formation. Using 16 human PDAC cell lines in a murine orthotopic PDAC model, local infiltration and metastatic spread were assessed by standardized dissemination scores. The cell lines were further classified into 3 hierarchical groups according to their metastatic potential. Their mRNA and microRNA (miRNA) expression was profiled via mRNA-microarray as well as Taqman Low Density Array, and validated by single quantitative RT-PCR and Western blotting. In the highly metastatic group, a significant induction of EP300 targeting miRNAs miR-194 (fold change: 26.88), miR-200b (fold change: 61.65), miR-200c (fold change: 19.44) and miR-429 (fold change: 21.67) (p < 0.05) was detected. Corresponding to this, decreased expression of EP300 mRNA (p < 0.0001) and protein (p < 0.05) were detected in the highly metastatic PDAC cell lines with liver metastases compared to the nonmetastatic or marginally metastatic cell lines, while no correlation with local tumor growth was found. In conclusion, epigenetic alterations with upregulated EP300 targeting miRNAs miR-194, miR-200b, miR-200c and miR-429 are related to reduced EP300 mRNA and protein in PDAC. These results demonstrate that miRNAs might be able to modulate the expression of metastasis-specific suppressor genes and metastatic behavior in PDAC, suggesting diagnostic and therapeutic opportunities for EP300 and its targeting miRNAs in PDAC.

AB - Genetic and epigenetic alterations during development of pancreatic ductal adenocarcinomas (PDACs) are well known. This study investigates genetic and epigenetic data together with tumor biology to find specific alterations responsible for metastasis formation. Using 16 human PDAC cell lines in a murine orthotopic PDAC model, local infiltration and metastatic spread were assessed by standardized dissemination scores. The cell lines were further classified into 3 hierarchical groups according to their metastatic potential. Their mRNA and microRNA (miRNA) expression was profiled via mRNA-microarray as well as Taqman Low Density Array, and validated by single quantitative RT-PCR and Western blotting. In the highly metastatic group, a significant induction of EP300 targeting miRNAs miR-194 (fold change: 26.88), miR-200b (fold change: 61.65), miR-200c (fold change: 19.44) and miR-429 (fold change: 21.67) (p < 0.05) was detected. Corresponding to this, decreased expression of EP300 mRNA (p < 0.0001) and protein (p < 0.05) were detected in the highly metastatic PDAC cell lines with liver metastases compared to the nonmetastatic or marginally metastatic cell lines, while no correlation with local tumor growth was found. In conclusion, epigenetic alterations with upregulated EP300 targeting miRNAs miR-194, miR-200b, miR-200c and miR-429 are related to reduced EP300 mRNA and protein in PDAC. These results demonstrate that miRNAs might be able to modulate the expression of metastasis-specific suppressor genes and metastatic behavior in PDAC, suggesting diagnostic and therapeutic opportunities for EP300 and its targeting miRNAs in PDAC.

KW - Animals

KW - Blotting, Western

KW - Carcinoma, Pancreatic Ductal

KW - Cell Line, Tumor

KW - E1A-Associated p300 Protein

KW - Gene Expression Profiling

KW - Humans

KW - Male

KW - Mice

KW - Mice, Nude

KW - MicroRNAs

KW - Neoplasm Metastasis

KW - Oligonucleotide Array Sequence Analysis

KW - Pancreatic Neoplasms

KW - Reverse Transcriptase Polymerase Chain Reaction

U2 - 10.1002/ijc.24695

DO - 10.1002/ijc.24695

M3 - SCORING: Journal article

C2 - 19569050

VL - 126

SP - 114

EP - 124

JO - INT J CANCER

JF - INT J CANCER

SN - 0020-7136

IS - 1

ER -