Genomic structure and expression profile of LPHH1, a 7TM gene variably expressed in breast cancer cell lines.
AffiliationCRC Section of Molecular Genetics, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Wilmslow Road, Manchester, UK.
MetadataShow full item record
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.
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. Acta
JournalBiochimica et Biophysica Acta
- Isolation and characterization of a human homologue of the latrophilin gene from a region of 1p31.1 implicated in breast cancer.
- Authors: White GR, Varley JM, Heighway J
- Issue date: 1998 Dec 31
- Alternative splicing, expression, and genomic structure of the 3' region of the gene encoding the sarcolemmal-associated proteins (SLAPs) defines a novel class of coiled-coil tail-anchored membrane proteins.
- Authors: Wielowieyski PA, Sevinc S, Guzzo R, Salih M, Wigle JT, Tuana BS
- Issue date: 2000 Dec 8
- Structural analysis of the human RFC-1 gene encoding a folate transporter reveals multiple promoters and alternatively spliced transcripts with 5' end heterogeneity.
- Authors: Tolner B, Roy K, Sirotnak FM
- Issue date: 1998 May 12
- The human decorin gene: intron-exon organization, discovery of two alternatively spliced exons in the 5' untranslated region, and mapping of the gene to chromosome 12q23.
- Authors: Danielson KG, Fazzio A, Cohen I, Cannizzaro LA, Eichstetter I, Iozzo RV
- Issue date: 1993 Jan
- Alternative and aberrant messenger RNA splicing of the mdm2 oncogene in invasive breast cancer.
- Authors: Lukas J, Gao DQ, Keshmeshian M, Wen WH, Tsao-Wei D, Rosenberg S, Press MF
- Issue date: 2001 Apr 1