Reeve J G, Brinkman A, Hughes S, Mitchell J, Schwander J, Bleehen N M
Medical Research Council, Medical Research Council Center, Cambridge, England.
J Natl Cancer Inst. 1992 Apr 15;84(8):628-34. doi: 10.1093/jnci/84.8.628.
The presence of multiple, low-molecular-weight, insulinlike growth factor (IGF)-binding proteins in lung tumor cell-conditioned medium and lung cancer patient serum has been recently reported.
To begin to elucidate the genetic basis for these observations, the present study examines the expression by lung tumor cell lines of three IGF-binding protein genes, namely, IGFBP-1, IGFBP-2, and IGFBP-3. Since IGF-binding proteins are thought to modulate the biologic action of the IGFs, the relationship between the expression of IGF-binding protein genes and the genes encoding IGF-I and IGF-II also has been investigated.
Gene expression was studied in four small-cell lung cancer (SCLC) and three non-small-cell lung cancer (NSCLC) cell lines using Northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR) for IGFBP-1.
IGFBP-1 gene expression was detected by Northern blot analysis in one NSCLC cell line only. However, RT-PCR revealed that the IGFBP-1 gene was expressed in all four SCLC cell lines and in two of the three NSCLC lines. Northern blot analysis of IGFBP-2 gene expression demonstrated that all lung tumor cell lines expressed this gene. A low level of IGFBP-3 gene expression was detected in one SCLC cell line and in all three NSCLC cell lines. All lung tumor cell lines expressed the IGF-II gene as determined by Northern blot analysis. In marked contrast, none of the lines showed evidence of IGF-I gene expression using this method. However, RT-PCR revealed a low level of IGF-I gene expression in one SCLC and one NSCLC cell line only.
These observations indicate 1) that IGF-binding proteins secreted by lung tumors are encoded by at least three different genes; 2) that there may be a close association between IGF-II and IGFBP-2 gene expression, such that, where there is production of IGF-II, IGFBP-2 is the principal BP; and 3) that the IGF-II gene is more widely expressed than the IGF-I gene in human lung tumor cell lines.
最近有报道称，在肺肿瘤细胞条件培养基和肺癌患者血清中存在多种低分子量胰岛素样生长因子（IGF）结合蛋白。
为了开始阐明这些观察结果的遗传基础，本研究检测了三种IGF结合蛋白基因，即IGFBP - 1、IGFBP - 2和IGFBP - 3在肺肿瘤细胞系中的表达。由于IGF结合蛋白被认为可调节IGF的生物学作用，因此还研究了IGF结合蛋白基因表达与编码IGF - I和IGF - II的基因之间的关系。
使用Northern印迹分析和针对IGFBP - 1的逆转录聚合酶链反应（RT - PCR），在四种小细胞肺癌（SCLC）和三种非小细胞肺癌（NSCLC）细胞系中研究基因表达。
仅在一种NSCLC细胞系中通过Northern印迹分析检测到IGFBP - 1基因表达。然而，RT - PCR显示IGFBP - 1基因在所有四种SCLC细胞系以及三种NSCLC系中的两种中表达。对IGFBP - 2基因表达的Northern印迹分析表明，所有肺肿瘤细胞系均表达该基因。在一种SCLC细胞系和所有三种NSCLC细胞系中检测到低水平的IGFBP - 3基因表达。通过Northern印迹分析确定，所有肺肿瘤细胞系均表达IGF - II基因。与之形成鲜明对比的是，使用该方法没有一个细胞系显示出IGF - I基因表达的证据。然而，RT - PCR仅在一种SCLC和一种NSCLC细胞系中检测到低水平的IGF - I基因表达。
这些观察结果表明：1）肺肿瘤分泌的IGF结合蛋白由至少三种不同基因编码；2）IGF - II和IGFBP - 2基因表达之间可能存在密切关联，即，在产生IGF - II的情况下，IGFBP - 2是主要的结合蛋白；3）在人肺肿瘤细胞系中，IGF - II基因的表达比IGF - I基因更广泛。
