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SERPINB5 and AKAP12 - expression and promoter methylation of metastasis suppressor genes in pancreatic ductal adenocarcinoma

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SERPINB5 and AKAP12 - expression and promoter methylation of metastasis suppressor genes in pancreatic ductal adenocarcinoma. / Mardin, Wolf A; Petrov, Kostadin O; Enns, Andreas; Senninger, Norbert; Haier, Joerg; Mees, Soeren T.

in: BMC CANCER, Jahrgang 10, 2010, S. 549.

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

Harvard

Mardin, WA, Petrov, KO, Enns, A, Senninger, N, Haier, J & Mees, ST 2010, 'SERPINB5 and AKAP12 - expression and promoter methylation of metastasis suppressor genes in pancreatic ductal adenocarcinoma', BMC CANCER, Jg. 10, S. 549. https://doi.org/10.1186/1471-2407-10-549

APA

Mardin, W. A., Petrov, K. O., Enns, A., Senninger, N., Haier, J., & Mees, S. T. (2010). SERPINB5 and AKAP12 - expression and promoter methylation of metastasis suppressor genes in pancreatic ductal adenocarcinoma. BMC CANCER, 10, 549. https://doi.org/10.1186/1471-2407-10-549

Vancouver

Mardin WA, Petrov KO, Enns A, Senninger N, Haier J, Mees ST. SERPINB5 and AKAP12 - expression and promoter methylation of metastasis suppressor genes in pancreatic ductal adenocarcinoma. BMC CANCER. 2010;10:549. https://doi.org/10.1186/1471-2407-10-549

Bibtex

@article{d87fab0c2eb549b9bae93d364f686638,
title = "SERPINB5 and AKAP12 - expression and promoter methylation of metastasis suppressor genes in pancreatic ductal adenocarcinoma",
abstract = "BACKGROUND: Early metastasis and infiltration are survival limiting characteristics of pancreatic ductal adenocarcinoma (PDAC). Thus, PDAC is likely to harbor alterations in metastasis suppressor genes that may provide novel diagnostic and therapeutic opportunities. This study investigates a panel of metastasis suppressor genes in correlation to PDAC phenotype and examines promoter methylation for regulatory influence on metastasis suppressor gene expression and for its potential as a diagnostic tool.METHODS: Metastatic and invasive potential of 16 PDAC cell lines were quantified in an orthotopic mouse model and mRNA expression of 11 metastasis suppressor genes determined by quantitative RT-PCR. Analysis for promoter methylation was performed using methylation specific PCR and bisulfite sequencing PCR. Protein expression was determined by Western blot.RESULTS: In general, higher metastasis suppressor gene mRNA expression was not consistent with less aggressive phenotypes of PDAC. Instead, mRNA overexpression of several metastasis suppressor genes was found in PDAC cell lines vs. normal pancreatic RNA. Of the investigated metastasis suppressor genes, only higher AKAP12 mRNA expression was correlated with decreased metastasis (P < 0.05) and invasion scores (P < 0.01) while higher SERPINB5 mRNA expression was correlated with increased metastasis scores (P < 0.05). Both genes' promoters showed methylation, but only increased SERPINB5 methylation was associated with loss of mRNA and protein expression (P < 0.05). SERPINB5 methylation was also directly correlated to decreased metastasis scores (P < 0.05).CONCLUSIONS: AKAP12 mRNA expression was correlated to attenuated invasive and metastatic potential and may be associated with less aggressive phenotypes of PDAC while no such evidence was obtained for the remaining metastasis suppressor genes. Increased SERPINB5 mRNA expression was correlated to increased metastasis and mRNA expression was regulated by methylation. Thus, SERPINB5 methylation was directly correlated to metastasis scores and may provide a diagnostic tool for PDAC.",
keywords = "A Kinase Anchor Proteins, Animals, Biomarkers, Tumor, Carcinoma, Pancreatic Ductal, Cell Cycle Proteins, Cell Line, Tumor, DNA Methylation, Genes, Tumor Suppressor, Humans, Male, Mice, Mice, Nude, Neoplasm Metastasis, Neoplasm Transplantation, Pancreatic Neoplasms, Promoter Regions, Genetic, RNA, Messenger, Serpins",
author = "Mardin, {Wolf A} and Petrov, {Kostadin O} and Andreas Enns and Norbert Senninger and Joerg Haier and Mees, {Soeren T}",
year = "2010",
doi = "10.1186/1471-2407-10-549",
language = "English",
volume = "10",
pages = "549",
journal = "BMC CANCER",
issn = "1471-2407",
publisher = "BioMed Central Ltd.",

}

RIS

TY - JOUR

T1 - SERPINB5 and AKAP12 - expression and promoter methylation of metastasis suppressor genes in pancreatic ductal adenocarcinoma

AU - Mardin, Wolf A

AU - Petrov, Kostadin O

AU - Enns, Andreas

AU - Senninger, Norbert

AU - Haier, Joerg

AU - Mees, Soeren T

PY - 2010

Y1 - 2010

N2 - BACKGROUND: Early metastasis and infiltration are survival limiting characteristics of pancreatic ductal adenocarcinoma (PDAC). Thus, PDAC is likely to harbor alterations in metastasis suppressor genes that may provide novel diagnostic and therapeutic opportunities. This study investigates a panel of metastasis suppressor genes in correlation to PDAC phenotype and examines promoter methylation for regulatory influence on metastasis suppressor gene expression and for its potential as a diagnostic tool.METHODS: Metastatic and invasive potential of 16 PDAC cell lines were quantified in an orthotopic mouse model and mRNA expression of 11 metastasis suppressor genes determined by quantitative RT-PCR. Analysis for promoter methylation was performed using methylation specific PCR and bisulfite sequencing PCR. Protein expression was determined by Western blot.RESULTS: In general, higher metastasis suppressor gene mRNA expression was not consistent with less aggressive phenotypes of PDAC. Instead, mRNA overexpression of several metastasis suppressor genes was found in PDAC cell lines vs. normal pancreatic RNA. Of the investigated metastasis suppressor genes, only higher AKAP12 mRNA expression was correlated with decreased metastasis (P < 0.05) and invasion scores (P < 0.01) while higher SERPINB5 mRNA expression was correlated with increased metastasis scores (P < 0.05). Both genes' promoters showed methylation, but only increased SERPINB5 methylation was associated with loss of mRNA and protein expression (P < 0.05). SERPINB5 methylation was also directly correlated to decreased metastasis scores (P < 0.05).CONCLUSIONS: AKAP12 mRNA expression was correlated to attenuated invasive and metastatic potential and may be associated with less aggressive phenotypes of PDAC while no such evidence was obtained for the remaining metastasis suppressor genes. Increased SERPINB5 mRNA expression was correlated to increased metastasis and mRNA expression was regulated by methylation. Thus, SERPINB5 methylation was directly correlated to metastasis scores and may provide a diagnostic tool for PDAC.

AB - BACKGROUND: Early metastasis and infiltration are survival limiting characteristics of pancreatic ductal adenocarcinoma (PDAC). Thus, PDAC is likely to harbor alterations in metastasis suppressor genes that may provide novel diagnostic and therapeutic opportunities. This study investigates a panel of metastasis suppressor genes in correlation to PDAC phenotype and examines promoter methylation for regulatory influence on metastasis suppressor gene expression and for its potential as a diagnostic tool.METHODS: Metastatic and invasive potential of 16 PDAC cell lines were quantified in an orthotopic mouse model and mRNA expression of 11 metastasis suppressor genes determined by quantitative RT-PCR. Analysis for promoter methylation was performed using methylation specific PCR and bisulfite sequencing PCR. Protein expression was determined by Western blot.RESULTS: In general, higher metastasis suppressor gene mRNA expression was not consistent with less aggressive phenotypes of PDAC. Instead, mRNA overexpression of several metastasis suppressor genes was found in PDAC cell lines vs. normal pancreatic RNA. Of the investigated metastasis suppressor genes, only higher AKAP12 mRNA expression was correlated with decreased metastasis (P < 0.05) and invasion scores (P < 0.01) while higher SERPINB5 mRNA expression was correlated with increased metastasis scores (P < 0.05). Both genes' promoters showed methylation, but only increased SERPINB5 methylation was associated with loss of mRNA and protein expression (P < 0.05). SERPINB5 methylation was also directly correlated to decreased metastasis scores (P < 0.05).CONCLUSIONS: AKAP12 mRNA expression was correlated to attenuated invasive and metastatic potential and may be associated with less aggressive phenotypes of PDAC while no such evidence was obtained for the remaining metastasis suppressor genes. Increased SERPINB5 mRNA expression was correlated to increased metastasis and mRNA expression was regulated by methylation. Thus, SERPINB5 methylation was directly correlated to metastasis scores and may provide a diagnostic tool for PDAC.

KW - A Kinase Anchor Proteins

KW - Animals

KW - Biomarkers, Tumor

KW - Carcinoma, Pancreatic Ductal

KW - Cell Cycle Proteins

KW - Cell Line, Tumor

KW - DNA Methylation

KW - Genes, Tumor Suppressor

KW - Humans

KW - Male

KW - Mice

KW - Mice, Nude

KW - Neoplasm Metastasis

KW - Neoplasm Transplantation

KW - Pancreatic Neoplasms

KW - Promoter Regions, Genetic

KW - RNA, Messenger

KW - Serpins

U2 - 10.1186/1471-2407-10-549

DO - 10.1186/1471-2407-10-549

M3 - SCORING: Journal article

C2 - 20939879

VL - 10

SP - 549

JO - BMC CANCER

JF - BMC CANCER

SN - 1471-2407

ER -