Linked Life Data

15105437

Source:http://linkedlifedata.com/resource/pubmed/id/15105437

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-6-28
pubmed:abstractText
To determine mechanisms for pituitary neoplasia we used methylation-sensitive arbitrarily primed-PCR to isolate novel genes that are differentially methylated relative to normal pituitary. We report the isolation of a novel differentially methylated chromosome 22 CpG island-associated gene (C22orf3). Sodium bisulfite sequencing of pooled tumor cohorts, used in the isolation of this gene, showed that only a proportion of the adenomas within the pools were methylated; however, expression analysis by quantitative RT-PCR of individual adenoma irrespective of subtype showed the majority (30 of 38; 79%) failed to express this gene relative to normal pituitary. Sodium bisulfite sequencing of individual adenomas showed that 6 of 30 (20%) that failed to express pituitary tumor apoptosis gene (PTAG) were methylated; however, genetic change as determined by loss of heterozygosity and sequence analysis was not apparent in the remaining tumors that failed to express this gene. In those cases where the CpG island of these genes was methylated it was invariably associated with loss of transcript expression. Enforced expression of C22orf3 in AtT20 cells had no measurable effects on cell proliferation or viability; however, in response to bromocriptine challenge (10-40 microm) cells expressing this gene showed a significantly augmented apoptotic response as determined by both acridine orange staining and TUNEL labeling. The apoptotic response to bromocriptine challenge was inhibited in coincubation experiments with the general caspase inhibitor z-VAD-fmk. In addition, in time course experiments, direct measurement of active caspases by fluorochrome-labeled inhibition of caspases, showed an augmented increase (approximately 2.4 fold) in active caspases in response to bromocriptine challenge in cells expressing C22orf3 relative to those harboring an empty vector control. The pituitary tumor derivation and its role in apoptosis of this gene led us to assign the acronym PTAG to this gene and its protein product. The ability of cells, showing reduced expression of PTAG, to evade or show a blunted apoptotic response may underlie oncogenic transformation in both the pituitary and other tumor types.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1827-39
pubmed:dateRevised
2007-6-2
pubmed:meshHeading
pubmed-meshheading:15105437-Adenoma, pubmed-meshheading:15105437-Amino Acid Chloromethyl Ketones, pubmed-meshheading:15105437-Apoptosis, pubmed-meshheading:15105437-Apoptosis Regulatory Proteins, pubmed-meshheading:15105437-Caspases, pubmed-meshheading:15105437-Cell Death, pubmed-meshheading:15105437-Chromosomes, Human, Pair 22, pubmed-meshheading:15105437-CpG Islands, pubmed-meshheading:15105437-Cysteine Proteinase Inhibitors, pubmed-meshheading:15105437-DNA Methylation, pubmed-meshheading:15105437-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15105437-Humans, pubmed-meshheading:15105437-Loss of Heterozygosity, pubmed-meshheading:15105437-Neoplasm Proteins, pubmed-meshheading:15105437-Pituitary Neoplasms, pubmed-meshheading:15105437-Sequence Analysis, pubmed-meshheading:15105437-Tumor Cells, Cultured
pubmed:year
2004
pubmed:articleTitle
Isolation and characterization of a novel pituitary tumor apoptosis gene.
pubmed:affiliation
Institute for Science and Technology in Medicine, Medical Research Unit, School of Postgraduate Medicine, Keele University, North Staffordshire Hospital, Stoke-on-Trent ST4 7QB, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't