Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2001-11-5
pubmed:abstractText
A cDNA clone encoding human SRBC [serum deprivation response factor (sdr)-related gene product that binds to c-kinase] was isolated in a yeast two-hybrid screening, with amino acids 1-304 of BRCA1 as the probe. The human SRBC gene (hSRBC) was mapped to chromosome region 11p15.5-p15.4, close to marker D11S1323, at which frequent loss of heterozygosity (LOH) has been observed in sporadic breast, lung, ovarian, and other types of adult cancers as well as childhood tumors. hSRBC-coding region mutations including frame shift and truncation mutations were detected in a few ovarian and lung cancer cell lines. More significantly, the expression of hSRBC protein was down-regulated in a large fraction [30 (70%) of 43] of breast, lung, and ovarian cancer cell lines, whereas strong expression of hSRBC protein was detected in normal mammary and lung epithelial cells. The down-regulation of hSRBC expression in cancer cells was associated with hypermethylation of CpG dinucleotides in its promoter region, and 3 (60%) of 5 primary breast tumors and 11 (79%) of 14 primary lung tumors were also found to be hypermethylated. Treatment of breast cancer MCF7 cells with 5'azacytidine and Trichostatin A resulted in expression of hSRBC, confirming DNA methylation as the mode of inactivation. Our results suggest that epigenetic or mutational inactivation of hSRBC may contribute to the pathogenesis of several types of human cancers, marking hSRBC as a candidate tumor suppressor gene.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7943-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11691816-Amino Acid Sequence, pubmed-meshheading:11691816-Animals, pubmed-meshheading:11691816-Base Sequence, pubmed-meshheading:11691816-Breast Neoplasms, pubmed-meshheading:11691816-Carrier Proteins, pubmed-meshheading:11691816-Chickens, pubmed-meshheading:11691816-Chromosomes, Human, Pair 11, pubmed-meshheading:11691816-DNA Methylation, pubmed-meshheading:11691816-Down-Regulation, pubmed-meshheading:11691816-Gene Expression Regulation, Neoplastic, pubmed-meshheading:11691816-Gene Silencing, pubmed-meshheading:11691816-Genes, Tumor Suppressor, pubmed-meshheading:11691816-Humans, pubmed-meshheading:11691816-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:11691816-Lung Neoplasms, pubmed-meshheading:11691816-Mice, pubmed-meshheading:11691816-Molecular Sequence Data, pubmed-meshheading:11691816-Mutation, pubmed-meshheading:11691816-Promoter Regions, Genetic, pubmed-meshheading:11691816-RNA, Messenger, pubmed-meshheading:11691816-Radiation Hybrid Mapping, pubmed-meshheading:11691816-Rats, pubmed-meshheading:11691816-Sequence Homology, Amino Acid
pubmed:year
2001
pubmed:articleTitle
Inactivation of human SRBC, located within the 11p15.5-p15.4 tumor suppressor region, in breast and lung cancers.
pubmed:affiliation
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, 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