Martinerie C, Viegas-Pequignot E, Nguyen V C, Perbal B
Laboratoire d'Oncologie Virale et Moléculaire, UFR de Biochimie, Université, Paris, Diderot, France.
Mol Pathol. 1997 Dec;50(6):310-6. doi: 10.1136/mp.50.6.310.
To characterise the human cyr61 gene (cyr61H) and determine its chromosomal locality. To compare expression of cyr61H in human tumour cell lines with that of two other structurally related genes, novH (nephroblastoma overexpressed gene) and CTGF (connective tissue growth factor), that are likely to play a role in the control of cell proliferation and differentiation.
To isolate the human cyr61 gene, placental genomic and 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 and in situ hybridisation on chromosomes were performed to map the cyr61H gene. Expression of cyr61H, novH, CTGF, and novH was analysed by northern blotting in both human neuroblastomas and glioblastoma cell lines.
Genomic and cDNA clones encompassing the cyr61H gene were isolated and characterised. Comparison of mouse and human cyr61 sequences indicated that their genomic organisation is highly conserved. Alignment of coding sequences highlighted the conservation of cyr61 regions that might be critical for its biological function. The data showed that the cyr61H gene is assigned to chromosome 1p22.3 and that different levels of cyr61H, CTGF, and novH mRNA have been detected in several human tumour cell lines derived from the nervous system.
The human cyr61 gene belongs to an emerging family of genes including CTGF/fisp12 and nov. The murine cyr61 encodes an extracellular cysteine rich protein that exhibits chemotactic activity, promotes attachment and spreading of cells, and potentiates the mitogenic effect of growth factors. Assignment of the cyr61H gene to chromosome 1p22.3 will allow studies to determine whether human pathologies derived from the nervous system or from other tissues are associated with chromosomal abnormalities involving this region. Although the coding regions of cyr61H, CTGF, 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 element in determining the stage of differentiation and/or the malignant potential of tumour cells.
鉴定人类cyr61基因（cyr61H）并确定其染色体定位。比较cyr61H在人类肿瘤细胞系中的表达与另外两个结构相关基因novH（肾母细胞瘤过度表达基因）和CTGF（结缔组织生长因子）的表达，这两个基因可能在细胞增殖和分化控制中发挥作用。
为分离人类cyr61基因，用鼠cyr61 cDNA筛选胎盘基因组文库和HeLa cDNA文库。确定完整cyr61H cDNA的核苷酸序列。进行一组体细胞杂种的Southern印迹分析和染色体原位杂交以定位cyr61H基因。通过Northern印迹分析人类神经母细胞瘤和胶质母细胞瘤细胞系中cyr61H、novH、CTGF和novH的表达。
分离并鉴定了包含cyr61H基因的基因组和cDNA克隆。小鼠和人类cyr61序列的比较表明它们的基因组组织高度保守。编码序列的比对突出了cyr61中可能对其生物学功能至关重要的区域的保守性。数据表明cyr61H基因定位于1p22.3染色体，并且在几种源自神经系统的人类肿瘤细胞系中检测到了不同水平的cyr61H、CTGF和novH mRNA。
人类cyr61基因属于一个新兴的基因家族，包括CTGF/fisp12和nov。鼠cyr61编码一种富含细胞外半胱氨酸的蛋白质，该蛋白质具有趋化活性，促进细胞附着和铺展，并增强生长因子的促有丝分裂作用。将cyr61H基因定位于1p22.3染色体将有助于开展研究，以确定源自神经系统或其他组织的人类病理学是否与涉及该区域的染色体异常相关。尽管cyr61H、CTGF和novH的编码区域高度同源，但越来越多的证据表明这些基因的表达受到差异调节，并且这些基因表达之间的平衡可能是决定肿瘤细胞分化阶段和/或恶性潜能的关键因素。
