Linked Life Data

9192806

Source:http://linkedlifedata.com/resource/pubmed/id/9192806

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1997-7-15
pubmed:abstractText
The E2F group of transcription factors transactivates genes that promote progression through the G1-S transition of the cell cycle. Members of the retinoblastoma (Rb) family of proteins bind to E2Fs and inhibit this function. E2F-4, one example of the E2F group, functions as an oncogene when transfected into nontransformed cells in vitro. On the other hand, mice that are homozygously lacking a normal E2F-1 gene develop cancers, consistent with a tumor-suppressive role for this gene. The exact function of E2Fs has thus been unclear; moreover, direct involvement of this gene in primary human tumorigenesis has not been shown. We, therefore, investigated mutation within the E2F-4 coding region in 16 primary gastric adenocarcinomas, 12 ulcerative colitis-associated neoplasms, 46 sporadic colorectal carcinomas, 9 endometrial cancers, and 3 prostatic carcinomas. We limited our investigation to the serine repeat within E2F-4, reasoning that this tract might be altered in genetically unstable tumors (replication error-positive, or RER+). All tumors were RER+, with the exception of a control group of 15 RER- sporadic colorectal carcinomas. PCR with incorporation of [32P]dCTP was performed using primers flanking the serine trinucleotide (AGC) repeat. Twenty-two of 59 gastrointestinal tumors (37%) contained E2F-4 mutations; these comprised 5 of 16 gastric tumors (31%), 4 of 12 ulcerative colitis-associated neoplasms (33%, including 1 dysplastic lesion), and 13 of 31 sporadic colorectal cancers (42%). No mutation was present in any of the endometrial, prostate, or RER- colorectal tumors. Of note, homozygous mutations occurred in three cases, and two of seven informative patients showed loss of one E2F-4 allele in their tumors. Furthermore, the RER+ sporadic colorectal tumors were evaluated at trinucleotide repeats within the genes for N-cadherin and B-catenin; no tumors demonstrated mutation of these genes. These data suggest that E2F-4 is a target of defective DNA repair in these tumors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2350-3
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9192806-Adenocarcinoma, pubmed-meshheading:9192806-Alleles, pubmed-meshheading:9192806-Cadherins, pubmed-meshheading:9192806-Chromosome Deletion, pubmed-meshheading:9192806-Cytoskeletal Proteins, pubmed-meshheading:9192806-DNA, Neoplasm, pubmed-meshheading:9192806-DNA-Binding Proteins, pubmed-meshheading:9192806-E2F4 Transcription Factor, pubmed-meshheading:9192806-Endometrial Neoplasms, pubmed-meshheading:9192806-Female, pubmed-meshheading:9192806-Gastrointestinal Neoplasms, pubmed-meshheading:9192806-Heterozygote, pubmed-meshheading:9192806-Humans, pubmed-meshheading:9192806-Male, pubmed-meshheading:9192806-Mutation, pubmed-meshheading:9192806-Prostatic Neoplasms, pubmed-meshheading:9192806-Trans-Activators, pubmed-meshheading:9192806-Transcription Factors, pubmed-meshheading:9192806-beta Catenin
pubmed:year
1997
pubmed:articleTitle
Frequent mutation of the E2F-4 cell cycle gene in primary human gastrointestinal tumors.
pubmed:affiliation
Department of Medicine, University of Maryland School of Medicine and Baltimore Veterans Affairs Medical Center, 21201-1595, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't