Linked Life Data

15289340

Source:http://linkedlifedata.com/resource/pubmed/id/15289340

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2004-8-3
pubmed:abstractText
Hypoxic conditions exist within pancreatic adenocarcinoma, yet pancreatic cancer cells survive and replicate within this environment. To understand the mechanisms involved in pancreatic cancer adaptation to hypoxia, we analyzed expression of a regulator of hypoxia-induced cell death, Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3). We found that BNIP3 was down-regulated in nine of nine pancreatic adenocarcinomas compared with normal pancreas despite the up-regulation of other hypoxia-inducible genes, including glucose transporter-1 and insulin-like growth factor-binding protein 3. Also, BNIP3 expression was undetectable even after hypoxia treatment in six of seven pancreatic cancer cell lines. The BNIP3 promoter, which was remarkably activated by hypoxia, is located within a CpG island. The methylation status of CpG dinucleotides within the BNIP3 promoter was analyzed after bisulfite treatment by sequencing and methylation-specific PCR. Hypermethylation of the BNIP3 promoter was observed in all BNIP3-negative pancreatic cancer cell lines and eight of 10 pancreatic adenocarcinoma samples. Treatment of BNIP3-negative pancreatic cancer cell lines with a DNA methylation inhibitor, 5-aza-2' deoxycytidine, restored hypoxia-induced BNIP3 expression. BNIP3 expression was also restored by introduction of a construct consisting of a full-length BNIP3 cDNA regulated by a cloned BNIP3 promoter. Restoration of BNIP3 expression rendered the pancreatic cancer cells notably more sensitive to hypoxia-induced cell death. In conclusion, down-regulation of BNIP3 by CpG methylation likely contributes to resistance to hypoxia-induced cell death in pancreatic cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5338-46
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15289340-Adenocarcinoma, pubmed-meshheading:15289340-Apoptosis, pubmed-meshheading:15289340-Azacitidine, pubmed-meshheading:15289340-Cell Hypoxia, pubmed-meshheading:15289340-CpG Islands, pubmed-meshheading:15289340-DNA Methylation, pubmed-meshheading:15289340-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15289340-Gene Silencing, pubmed-meshheading:15289340-Glucose Transport Proteins, Facilitative, pubmed-meshheading:15289340-Humans, pubmed-meshheading:15289340-Insulin-Like Growth Factor Binding Protein 3, pubmed-meshheading:15289340-Membrane Proteins, pubmed-meshheading:15289340-Monosaccharide Transport Proteins, pubmed-meshheading:15289340-Pancreas, pubmed-meshheading:15289340-Pancreatic Neoplasms, pubmed-meshheading:15289340-Promoter Regions, Genetic, pubmed-meshheading:15289340-Proto-Oncogene Proteins, pubmed-meshheading:15289340-Tumor Cells, Cultured
pubmed:year
2004
pubmed:articleTitle
Silencing of the hypoxia-inducible cell death protein BNIP3 in pancreatic cancer.
pubmed:affiliation
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109-0622, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't