Isolation and characterization of a human homologue of the latrophilin gene from a region of 1p31.1 implicated in breast cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/93114
Title:
Isolation and characterization of a human homologue of the latrophilin gene from a region of 1p31.1 implicated in breast cancer.
Authors:
White, Gavin R M; Varley, Jennifer; Heighway, Jim
Abstract:
We have identified a region of chromosome 1p31.1 that shows high frequency loss of heterozygosity (LOH) in human breast cancer. This region forms part of a 7 Mb YAC/BAC contig. In order to identify candidate sequences, mutation of which might contribute to the development of disease, we have carried out mapping studies of ESTs localized to 1p31.1. This analysis, coupled with library screening and a modified 5' RACE-PCR strategy, resulted in the identification and characterization of a novel gene (LPHH1) which is located adjacent to the smallest region of overlapping loss (SRO) seen in tumours. The 4209 bp open reading frame of the 7 kb LPHH1 transcript encodes a peptide which shows approximately 65% identity to rat latrophilin, a G-coupled, seven span transmembrane protein, which binds alpha-latrotoxin. In the human sequence, whilst conservation of the transmembrane domain is high, the intra- and extracellular domains show two regions of variable structure, which are presumably generated by alternative splicing. Surprisingly, while expression of the rat gene is tightly restricted to neurological and perhaps some endocrine cells, the human sequence appears to be expressed very widely in all normal tissues tested. Northern and RT-PCR analysis of a panel of tumour cell lines showed that LPHH1 expression was variable, apparently elevated in some lines and absent or markedly reduced in others. Furthermore, characterization of the range of transcripts encoded in a breast tumour cell line, compared to normal breast, suggested that gene product variability was higher in the tumour.
Affiliation:
CRC Section of Molecular Genetics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Isolation and characterization of a human homologue of the latrophilin gene from a region of 1p31.1 implicated in breast cancer. 1998, 17 (26):3513-9 Oncogene
Journal:
Oncogene
Issue Date:
31-Dec-1998
URI:
http://hdl.handle.net/10541/93114
DOI:
10.1038/sj.onc.1202487
PubMed ID:
10030676
Type:
Article
Language:
en
ISSN:
0950-9232
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorWhite, Gavin R Men
dc.contributor.authorVarley, Jenniferen
dc.contributor.authorHeighway, Jimen
dc.date.accessioned2010-02-25T16:51:01Z-
dc.date.available2010-02-25T16:51:01Z-
dc.date.issued1998-12-31-
dc.identifier.citationIsolation and characterization of a human homologue of the latrophilin gene from a region of 1p31.1 implicated in breast cancer. 1998, 17 (26):3513-9 Oncogeneen
dc.identifier.issn0950-9232-
dc.identifier.pmid10030676-
dc.identifier.doi10.1038/sj.onc.1202487-
dc.identifier.urihttp://hdl.handle.net/10541/93114-
dc.description.abstractWe have identified a region of chromosome 1p31.1 that shows high frequency loss of heterozygosity (LOH) in human breast cancer. This region forms part of a 7 Mb YAC/BAC contig. In order to identify candidate sequences, mutation of which might contribute to the development of disease, we have carried out mapping studies of ESTs localized to 1p31.1. This analysis, coupled with library screening and a modified 5' RACE-PCR strategy, resulted in the identification and characterization of a novel gene (LPHH1) which is located adjacent to the smallest region of overlapping loss (SRO) seen in tumours. The 4209 bp open reading frame of the 7 kb LPHH1 transcript encodes a peptide which shows approximately 65% identity to rat latrophilin, a G-coupled, seven span transmembrane protein, which binds alpha-latrotoxin. In the human sequence, whilst conservation of the transmembrane domain is high, the intra- and extracellular domains show two regions of variable structure, which are presumably generated by alternative splicing. Surprisingly, while expression of the rat gene is tightly restricted to neurological and perhaps some endocrine cells, the human sequence appears to be expressed very widely in all normal tissues tested. Northern and RT-PCR analysis of a panel of tumour cell lines showed that LPHH1 expression was variable, apparently elevated in some lines and absent or markedly reduced in others. Furthermore, characterization of the range of transcripts encoded in a breast tumour cell line, compared to normal breast, suggested that gene product variability was higher in the tumour.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectCultured Tumour Cellsen
dc.subjectCancerous Gene Expression Regulationen
dc.subject.meshAmino Acid Sequence-
dc.subject.meshAnimals-
dc.subject.meshBase Sequence-
dc.subject.meshBreast Neoplasms-
dc.subject.meshCloning, Molecular-
dc.subject.meshDNA, Complementary-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshHumans-
dc.subject.meshMembrane Proteins-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshRats-
dc.subject.meshReceptors, G-Protein-Coupled-
dc.subject.meshReceptors, Peptide-
dc.subject.meshReference Values-
dc.subject.meshSequence Analysis-
dc.subject.meshTumor Cells, Cultured-
dc.titleIsolation and characterization of a human homologue of the latrophilin gene from a region of 1p31.1 implicated in breast cancer.en
dc.typeArticleen
dc.contributor.departmentCRC Section of Molecular Genetics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalOncogeneen
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