Identification of maspin and s100p as novel hypomethylation targets in pancreatic cancer using global gene expression profiling

ABSTRACT DNA hypomethylation is one of the major epigenetic alterations in human cancers. We have previously shown that genes identified as hypomethylated in pancreatic cancer are expressed

in pancreatic cancer cell lines, but not in normal pancreatic ductal epithelium and can be reexpressed in nonexpressing cells using ‘epigenetic modifying agents’ such as DNA

methyltransferase inhibitors. To identify additional targets for aberrant hypomethylation in pancreatic cancer, we used oligonucleotide microarrays to screen for genes that displayed

expression patterns associated with hypomethylation. This analysis identified a substantial number of candidates including previously reported hypomethylated genes. A subset of eight genes

were selected for further methylation analysis, and two cancer-related genes, _maspin_ and _S100P_, were found to be aberrantly hypomethylated in a large fraction of pancreatic cancer cell

lines and primary pancreatic carcinomas. Combined treatment with 5-aza-2′-deoxycytidie and trichostatin A resulted in synergistic induction of _maspin_ and _S100P_ mRNA in MiaPaCa2 cells

where both genes were methylated. Furthermore, there was an inverse correlation between methylation and mRNA expression level for _maspin_ and _S100P_ in a large panel of pancreatic cancer

cell lines. We also found a significant difference in the methylation patterns of _maspin_ and two previously identified hypomethylated genes (_trefoil factor 2_ and _lipocalin 2_) between

pancreatic and breast cancer cell lines, suggesting cancer-type specificity for some hypomethylation patterns. Thus, our present results confirm that DNA hypomethylation is a frequent

epigenetic event in pancreatic cancer, and suggest that gene expression profiling may help to identify potential targets affected by this epigenetic alteration. Access through your

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BEING VIEWED BY OTHERS GENOME-WIDE DNA METHYLATION PROFILING REVEALS A NOVEL HYPERMETHYLATED BIOMARKER _PRKCB_ IN GASTRIC CANCER Article Open access 04 November 2024 DNA METHYLATION PATTERNS

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Open access 23 June 2020 ABBREVIATIONS * 5Aza-dC: 5-aza-2′-deoxycytidine * TSA: trichostatin A * MSP: methylation-specific PCR * RT–PCR: reverse transcription–PCR REFERENCES * Bachman KE,

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6051–6054. Download references ACKNOWLEDGEMENTS This work was supported by the SPORE in Gastrointestinal Malignancies (CA62924), the Grant CA90709, and the Michael Rolfe Foundation. We thank

Dr Scott E Kern (The Johns Hopkins Medical Institutions, Baltimore, MD, USA) for providing the DNA samples from pancreatic cancer xenografts and Dr Mieke Schutte (University Hospital

Rotterdam, The Netherlands) for providing DNA samples from breast cancer cell lines. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Pathology, The Johns Hopkins Medical

Institutions, Baltimore, MD, USA Norihiro Sato, Noriyoshi Fukushima, Hiroyuki Matsubayashi & Michael Goggins * Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore,

MD, USA Michael Goggins * Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD, USA Michael Goggins Authors * Norihiro Sato View author publications You can also

search for this author inPubMed Google Scholar * Noriyoshi Fukushima View author publications You can also search for this author inPubMed Google Scholar * Hiroyuki Matsubayashi View author

publications You can also search for this author inPubMed Google Scholar * Michael Goggins View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING

AUTHOR Correspondence to Michael Goggins. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Sato, N., Fukushima, N., Matsubayashi, H. _et al._

Identification of _maspin_ and _S100P_ as novel hypomethylation targets in pancreatic cancer using global gene expression profiling. _Oncogene_ 23, 1531–1538 (2004).

https://doi.org/10.1038/sj.onc.1207269 Download citation * Received: 18 August 2003 * Revised: 10 October 2003 * Accepted: 10 October 2003 * Published: 29 December 2003 * Issue Date: 26

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_SERPINB5_ * _S100P_ * microarray