Bradshaw S L, Naus C C, Zhu D, Kidder G M, Han V K
Department of Pediatrics, University of Western Ontario, Canada.
Growth Regul. 1993 Mar;3(1):26-9.
When C6 glioma cells are stably transfected with a connexin43 cDNA and the gene overexpressed, the rate of cellular proliferation is decreased. To determine if this phenomenon is related to alterations in IGFBP synthesis, we have compared the conditioned media of primary rat astroglia, C6, clones Cx43-13 (high expresser of the transfected connexin43 gene), and Cx43-12 and Cx43-14 (intermediate expressers). Primary astroglia produced IGFBP-2 (M(r) 34 K) and IGFBP-3 (40-45 K). C6 cells synthesized high levels of IGFBP-3 and low levels of IGFBP-2, and a 24 K IGFBP (IGFBP-4). Cx43-13 cells did not synthesize IGFBP-3, but produced low levels of IGFBP-2 and high levels of IGFBP-4. Cx43-12 and Cx43-14 secreted IGFBP profiles similar to the parent C6 line, but with reduced levels of IGFBP-2. Northern analysis showed the changes in IGFBPs in the conditioned media to be correlated with alterations in stable mRNA levels. IGFBP-4, a inhibitor of IGF biological action, was produced in greater quantities by the slowly proliferating Cx43-13 cells. Alterations in IGFBP-4 synthesis may be responsible, at least in part, for the reduced proliferative capacity in cells with abundant connexin43.
当C6胶质瘤细胞用连接蛋白43 cDNA稳定转染并使该基因过表达时，细胞增殖速率降低。为了确定这种现象是否与胰岛素样生长因子结合蛋白（IGFBP）合成的改变有关，我们比较了原代大鼠星形胶质细胞、C6细胞、克隆Cx43 - 13（转染的连接蛋白43基因的高表达细胞）以及Cx43 - 12和Cx43 - 14（中等表达细胞）的条件培养基。原代星形胶质细胞产生IGFBP - 2（分子量34K）和IGFBP - 3（40 - 45K）。C6细胞合成高水平的IGFBP - 3和低水平的IGFBP - 2，以及一种24K的IGFBP（IGFBP - 4）。Cx43 - 13细胞不合成IGFBP - 3，但产生低水平的IGFBP - 2和高水平的IGFBP - 4。Cx43 - 12和Cx43 - 14分泌的IGFBP谱与亲本C6细胞系相似，但IGFBP - 2水平降低。Northern分析表明，条件培养基中IGFBPs的变化与稳定mRNA水平的改变相关。IGFBP - 4是IGF生物学作用的抑制剂，在增殖缓慢的Cx43 - 13细胞中产生量更多。IGFBP - 4合成的改变可能至少部分地导致了连接蛋白43丰富的细胞增殖能力降低。
