Genomic structure and expression profile of LPHH1, a 7TM gene variably expressed in breast cancer cell lines.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86120
Title:
Genomic structure and expression profile of LPHH1, a 7TM gene variably expressed in breast cancer cell lines.
Authors:
White, Gavin R M; Varley, Jennifer; Heighway, Jim
Abstract:
Gene identification studies, centred on a region of overlapping loss of heterozygosity in breast tumours within band 1p31.1, lead to the characterisation of LPHH1, a novel human 7TM gene. The coding sequence of LPHH1 extends over a 60 kb region and comprises in excess of 28 exons. Alternative splicing occurs minimally at five positions, four of which are within the coding sequence. The fifth region of alternative splicing occurs at the extreme 5' end of the transcript. A clear tissue specific bias in alternative exon selection is observed to some degree at all five positions, including the extreme 5' region, which raises the possibility of multiple and perhaps tissue specific promoters. One such putative promoter region, which appears to be utilised predominantly in breast cancer cells, has been identified. LPHH1 is highly evolutionarily conserved, with the simplest (19 exon) gene product being 95% identical between human and rat. Comparison of the alternatively spliced exons between three species, where data are available, has so far revealed 100% identity in the encoded peptide sequences, suggesting conservation of a functional aspect of this splicing. Gene expression has been observed in all tissues and cell lines tested, with the exception of lymphoblastoid and multiple myeloma lines, where there appears to be only a very low level of transcription. LPHH1 also appears to be downregulated in human bone marrow. These data are consistent with a role for the gene products in adhesion-mediated signalling. Analysis of a panel of breast tumour cell lines revealed that a number apparently overexpressed the gene whilst others showed very low levels of transcription. In one case, the overexpression correlated with a low level increase in gene copy number in the tumour line. In addition to differences in the overall levels of expression, LPHH1 mRNAs were alternatively spliced to varying degrees with shifts in the major gene product to truncated or altered forms in some lines. No somatic LPHH1 mutations were detected through sequence analysis of four primary breast tumours that showed loss of the adjacent 1p31.1 marker D1S207.
Affiliation:
CRC Section of Molecular Genetics, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Wilmslow Road, Manchester, UK.
Citation:
Genomic structure and expression profile of LPHH1, a 7TM gene variably expressed in breast cancer cell lines. 2000, 1491 (1-3):75-92 Biochim. Biophys. Acta
Journal:
Biochimica et Biophysica Acta
Issue Date:
25-Apr-2000
URI:
http://hdl.handle.net/10541/86120
PubMed ID:
10760572
Type:
Article
Language:
en
ISSN:
0006-3002
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.accessioned2009-11-13T12:54:04Z-
dc.date.available2009-11-13T12:54:04Z-
dc.date.issued2000-04-25-
dc.identifier.citationGenomic structure and expression profile of LPHH1, a 7TM gene variably expressed in breast cancer cell lines. 2000, 1491 (1-3):75-92 Biochim. Biophys. Actaen
dc.identifier.issn0006-3002-
dc.identifier.pmid10760572-
dc.identifier.urihttp://hdl.handle.net/10541/86120-
dc.description.abstractGene identification studies, centred on a region of overlapping loss of heterozygosity in breast tumours within band 1p31.1, lead to the characterisation of LPHH1, a novel human 7TM gene. The coding sequence of LPHH1 extends over a 60 kb region and comprises in excess of 28 exons. Alternative splicing occurs minimally at five positions, four of which are within the coding sequence. The fifth region of alternative splicing occurs at the extreme 5' end of the transcript. A clear tissue specific bias in alternative exon selection is observed to some degree at all five positions, including the extreme 5' region, which raises the possibility of multiple and perhaps tissue specific promoters. One such putative promoter region, which appears to be utilised predominantly in breast cancer cells, has been identified. LPHH1 is highly evolutionarily conserved, with the simplest (19 exon) gene product being 95% identical between human and rat. Comparison of the alternatively spliced exons between three species, where data are available, has so far revealed 100% identity in the encoded peptide sequences, suggesting conservation of a functional aspect of this splicing. Gene expression has been observed in all tissues and cell lines tested, with the exception of lymphoblastoid and multiple myeloma lines, where there appears to be only a very low level of transcription. LPHH1 also appears to be downregulated in human bone marrow. These data are consistent with a role for the gene products in adhesion-mediated signalling. Analysis of a panel of breast tumour cell lines revealed that a number apparently overexpressed the gene whilst others showed very low levels of transcription. In one case, the overexpression correlated with a low level increase in gene copy number in the tumour line. In addition to differences in the overall levels of expression, LPHH1 mRNAs were alternatively spliced to varying degrees with shifts in the major gene product to truncated or altered forms in some lines. No somatic LPHH1 mutations were detected through sequence analysis of four primary breast tumours that showed loss of the adjacent 1p31.1 marker D1S207.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectCultured Tumour Cellsen
dc.subject.meshAlternative Splicing-
dc.subject.meshAnimals-
dc.subject.meshBase Sequence-
dc.subject.meshBrain-
dc.subject.meshBreast Neoplasms-
dc.subject.meshCattle-
dc.subject.meshDNA Primers-
dc.subject.meshExons-
dc.subject.meshGene Expression-
dc.subject.meshGene Library-
dc.subject.meshHumans-
dc.subject.meshIntrons-
dc.subject.meshMembrane Proteins-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshMutation-
dc.subject.meshOpen Reading Frames-
dc.subject.meshRats-
dc.subject.meshReceptors, G-Protein-Coupled-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshTumor Cells, Cultured-
dc.titleGenomic structure and expression profile of LPHH1, a 7TM gene variably expressed in breast cancer cell lines.en
dc.typeArticleen
dc.contributor.departmentCRC Section of Molecular Genetics, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Wilmslow Road, Manchester, UK.en
dc.identifier.journalBiochimica et Biophysica Actaen
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