CHROMOSOMAL MAPPING AND EXPRESSION OF THE HUMAN CYR61 GENE IN TUMOR-CELLS FROM THE NERVOUS-SYSTEM

Aims-To characterise the human cyr61 gene (cyr61H) and determine its c hromosomal locality. To compare expression of cyr61H in human tumour c ell lines with that of two other structurally related genes, novH (nep hroblastoma overexpressed gene) and CTGF (connective tissue growth fac tor), that are likely to play a role in the control of cell proliferat ion and differentiation. Methods-To isolate the human cyr61 gene, plac ental genomic and HeLa cDNA libraries were screened with murine cyr61 cDNA. The nucleotide sequence of the complete cyr61H cDNA was establis hed. Both Southern blotting of a panel of somatic cell hybrids and in situ hybridisation on chromosomes were performed to map the cyr61H gen e. Expression of cyr61H, novH, CTGF, and novH was analysed by northern blotting in both human neuroblastomas and glioblastoma cell lines. Re sults-Genomic and cDNA clones encompassing the cyr61H gene were isolat ed and characterised. Comparison of mouse and human cyr61 sequences in dicated that their genomic organisation is highly conserved. Alignment of coding sequences highlighted the conservation of cyr61 regions tha t might be critical for its biological function. The data showed that the cyr61H gene is assigned to chromosome 1p22.3 and that different le vels of cyr61H, CTGF, and novH mRNA have been detected in several huma n tumour cell lines derived from the nervous system. Conclusions-The h uman cyr61 gene belongs to an emerging family of genes including CTGF/ fisp12 and nov. The murine cyr61 encodes an extracellular cysteine ric h protein that exhibits chemotactic activity, promotes attachment and spreading of cells, and potentiates the mitogenic effect of growth fac tors. Assignment of the cyr61H gene to chromosome 1p22.3 will allow st udies to determine whether human pathologies derived from the nervous system or from other tissues are associated with chromosomal abnormali ties involving this region. Although the coding regions of cyr61H, CTG F, and novH are highly homologous, a growing body of evidence suggests that expression of these genes is regulated differentially, and that a balance between expression of these genes might represent a key elem ent in determining the stage of differentiation and/or the malignant p otential of tumour cells.