Linked Life Data

12170765

Source:http://linkedlifedata.com/resource/pubmed/id/12170765

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-8-12
pubmed:abstractText
Caspase-8 (CASP8) is an apoptosis inducing cysteine protease which is activated through the formation of a death-inducing signaling complex when death receptors are complexed to their specific ligands. Recent reports indicate that CASP8 expression is lost via a combination of promoter methylation and allelic loss in subset of neuroblastomas. We investigated the state of the gene in lung tumors and cell lines. RT-PCR studies indicated that gene expression was lost in most (27 of 34, 79%) of small cell lung carcinoma (SCLC) cell lines, but expression was retained in all 22 non-SCLC (NSCLC) lines tested. Loss of gene expression at the RNA level was associated with absent protein expression by Western blotting and lack of CASP8 enzymatic activity. Methylation of the promoter region of the CASP8 gene was present in 16 of 27 (59%) of the SCLC lines lacking gene expression. All methylated cell lines lacked the presence of an unmethylated allele indicating biallelic methylation or loss of non-methylated allele. Promoter methylation was absent in all SCLC and NSCLC cell lines retaining gene expression, and all of these lines had the unmethylated form of the gene. One non-expressing SCLC cell line, NCI-H82, had a homozygous deletion at 2q33 encompassing the chromosomal location of the CASP8 gene. The mechanism of gene inactivation in the remaining 10 of 27 (37%) non-expressing SCLC cell lines is unknown. Using five polymorphic markers for 2q33 a high frequency of allelic loss was present in SCLC lines. Analyses of fresh tumors showed that 15 of 43 (35%) of the SCLC, seven of 40 (18%) of bronchial carcinoids and none of 44 NSCLC tumors had CASP8 promoter methylation. Because only approximately 60% of SCLC cell lines lacking CASP8 expression were methylated, extrapolating from the cell line data, we estimate that approximately 58% of SCLC and 30% of bronchial carcinoids lack CASP8 expression. Thus, CASP8 expression is absent in a subset of both high grade (SCLC) and low grade (carcinoid) neuroendocrine lung tumors but not in NSCLC, which usually lack neuroendocrine features. CASP8 may function as a tumor suppressor gene in neuroendocrine lung tumors.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1538-4047
pubmed:author
pubmed:issnType
Print
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
65-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12170765-Apoptosis, pubmed-meshheading:12170765-Bronchial Neoplasms, pubmed-meshheading:12170765-Carcinoid Tumor, pubmed-meshheading:12170765-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:12170765-Carcinoma, Small Cell, pubmed-meshheading:12170765-Caspase 8, pubmed-meshheading:12170765-Caspase 9, pubmed-meshheading:12170765-Caspases, pubmed-meshheading:12170765-Chromosomes, Human, Pair 2, pubmed-meshheading:12170765-DNA, Neoplasm, pubmed-meshheading:12170765-DNA Methylation, pubmed-meshheading:12170765-Enzyme Induction, pubmed-meshheading:12170765-Gene Expression Regulation, Enzymologic, pubmed-meshheading:12170765-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12170765-Gene Silencing, pubmed-meshheading:12170765-Genes, Tumor Suppressor, pubmed-meshheading:12170765-Humans, pubmed-meshheading:12170765-Loss of Heterozygosity, pubmed-meshheading:12170765-Lung Neoplasms, pubmed-meshheading:12170765-Neoplasm Proteins
pubmed:articleTitle
Differential inactivation of caspase-8 in lung cancers.
pubmed:affiliation
Hamon Center for Therapeutic Oncology Research, Departments of Pathology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390-8593, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.