Linked Life Data

9850059

Source:http://linkedlifedata.com/resource/pubmed/id/9850059

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
1998-12-31
pubmed:abstractText
Transforming growth factor beta (TGF-beta) is an extracellular ligand that binds to a heterodimeric receptor, initiating signals that regulate growth, differentiation, and apoptosis. Many cancers, including pancreatic cancer, harbor defects in TGF-beta signaling and are resistant to TGF-beta-mediated growth suppression. Genetic alterations of DPC4, which encodes a DNA binding protein that is a downstream component of the pathway, most frequently occur in pancreatic and biliary carcinomas. We searched for other targets of mutation of the TGF-beta pathway in these cancers. We report somatic alterations of the TGF-beta type I receptor gene ALK-5. Homozygous deletions of ALK-5 were identified in 1 of 97 pancreatic and 1 of 12 biliary adenocarcinomas. A germ-line variant of ALK-5, presumably a polymorphism, was identified, but no somatic intragenic mutations were identified upon sequencing of all coding regions of ALK-5. Somatic alterations of the TGF-beta type II receptor gene (TGFBR2) were identified in 4 of 97 (4.1%) pancreas cancers, including a homozygous deletion in a replication error-negative cancer and three homozygous frameshift mutations of the poly(A) tract of the TGF-beta type II receptor in replication error-positive cancers. We also studied other related type I receptors of the TGF-beta superfamily. In a panel of pancreas cancers preselected for loss of heterozygosity at the ALK-1 locus, sequencing of all coding exons of the ALK-1 gene revealed no alterations. No homozygous deletions were detected in the ALK-1, ALK-2, ALK-3, or ALK-6 genes in a panel of 86 pancreatic cancer xenografts and 11 pancreatic cancer and 22 breast cancer cell lines. The rate of genetic inactivation of TGF-beta pathway members was determined in 45 pancreatic cancers. Eighty-two % of these pancreatic cancers had genetic inactivation of the DPC4, p15, ALK-5, or TGFBR2 genes. Our results indicate that the TGF-beta type I and type II receptor genes are selective targets of genetic inactivation in pancreatic and biliary cancers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5329-32
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9850059-Activin Receptors, pubmed-meshheading:9850059-Adenocarcinoma, pubmed-meshheading:9850059-Aged, pubmed-meshheading:9850059-Biliary Tract Neoplasms, pubmed-meshheading:9850059-Carcinoma, Ductal, Breast, pubmed-meshheading:9850059-DNA-Binding Proteins, pubmed-meshheading:9850059-Female, pubmed-meshheading:9850059-Genes, p16, pubmed-meshheading:9850059-Humans, pubmed-meshheading:9850059-Loss of Heterozygosity, pubmed-meshheading:9850059-Male, pubmed-meshheading:9850059-Middle Aged, pubmed-meshheading:9850059-Mutation, pubmed-meshheading:9850059-Pancreatic Neoplasms, pubmed-meshheading:9850059-Protein-Serine-Threonine Kinases, pubmed-meshheading:9850059-Receptors, Transforming Growth Factor beta, pubmed-meshheading:9850059-Smad4 Protein, pubmed-meshheading:9850059-Trans-Activators, pubmed-meshheading:9850059-Transforming Growth Factor beta
pubmed:year
1998
pubmed:articleTitle
Genetic alterations of the transforming growth factor beta receptor genes in pancreatic and biliary adenocarcinomas.
pubmed:affiliation
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.