Chromosomal mapping and expression of the human cyr61 gene in tumour cells from the nervous system.

C Martinerie, E Viegas-Pequignot, V C Nguyen, B Perbal

Laboratoire d'Oncologie Virale et Moléculaire, UFR de Biochimie, Université, Paris, Diderot, France.

AIMS: To characterise the human cyr61 gene (cyr61H) and determineits chromosomal locality. To compare expression of cyr61H inhuman tumour cell lines with that of two other structurallyrelated genes, novH (nephroblastoma overexpressed gene) andCTGF (connective tissue growth factor), that are likely to playa role in the control of cell proliferation and differentiation.METHODS: To isolate the human cyr61 gene, placental genomicand HeLa cDNA libraries were screened with murine cyr61 cDNA.The nucleotide sequence of the complete cyr61H cDNA was established.Both Southern blotting of a panel of somatic cell hybrids andin situ hybridisation on chromosomes were performed to map thecyr61H gene. Expression of cyr61H, novH, CTGF, and novH wasanalysed by northern blotting in both human neuroblastomas andglioblastoma cell lines. RESULTS: Genomic and cDNA clones encompassingthe cyr61H gene were isolated and characterised. Comparisonof mouse and human cyr61 sequences indicated that their genomicorganisation is highly conserved. Alignment of coding sequenceshighlighted the conservation of cyr61 regions that might becritical for its biological function. The data showed that thecyr61H gene is assigned to chromosome 1p22.3 and that differentlevels of cyr61H, CTGF, and novH mRNA have been detected inseveral human tumour cell lines derived from the nervous system.CONCLUSIONS: The human cyr61 gene belongs to an emerging familyof genes including CTGF/fisp12 and nov. The murine cyr61 encodesan extracellular cysteine rich protein that exhibits chemotacticactivity, promotes attachment and spreading of cells, and potentiatesthe mitogenic effect of growth factors. Assignment of the cyr61Hgene to chromosome 1p22.3 will allow studies to determine whetherhuman pathologies derived from the nervous system or from othertissues are associated with chromosomal abnormalities involvingthis region. Although the coding regions of cyr61H, CTGF, andnovH are highly homologous, a growing body of evidence suggeststhat expression of these genes is regulated differentially,and that a balance between expression of these genes might representa key element in determining the stage of differentiation and/orthe malignant potential of tumour cells.

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