Wulbrand U, Remmert G, Zöfel P, Wied M, Arnold R, Fehmann H C
Department of Internal Medicine, Philipps-University Marburg, Germany.
Eur J Clin Invest. 2000 Aug;30(8):729-39. doi: 10.1046/j.1365-2362.2000.00700.x.
Insulin-like growth factors (IGF) and their corresponding receptors and binding proteins are important in carcinogenesis for several tumours, but their expression pattern in the functionally and biologically heterogeneous human neuroendocrine tumours of the gastroenteropancreatic tract is largely unknown.
This study searched for the mRNA expression patterns of components of the IGF system: IGF-1 and IGF-2, IGF receptors 1 and 2 (IGF-1R, IGF-2R), IGF-binding proteins 1-6 (IGFBP1-6)) in the most frequent human gastroenteropancreatic neuroendocrine tumours (gastrinomas, insulinomas, tumours associated with carcinoid syndrome and functionally inactive tumours) employing reverse transcriptase-polymerase chain reaction (RT-PCR).
In the 37 tumour samples analysed (nine gastrinomas, 10 insulinomas, nine tumours associated with carcinoid syndrome and nine functionally inactive tumours) IGFBP-2 was found in all tumour samples while the IGFBP-1 was expressed only at low frequency (10-22%) among the four tumour types. The IGF-2R was predominantly expressed in gastrinomas. Among the four tumour types the expression of IGF-1R, IGF-2R and IGFBP-6 varied significantly. In addition, 12 pairs of significantly coexpressed IGF system components were detected (IGF-1 <--> IGF-1R, IGF-1 <--> IGF-2R, IGF-1 <--> IGFBP-3, IGF-1 <--> IGFBP-6, IGFBP-3 <--> IGF-1R, IGFBP-6 <--> IGF-1R, IGFBP-1 <--> IGF-2R, IGFBP-3 <--> IGF-2R, IGFBP-5 <--> IGF-2R, IGFBP-3 <--> IGFBP-5, IGFBP-3 <--> IGFBP-6, IGFBP-5 <--> IGFBP-6).
The described differences of the expression patterns of the IGF system components in neuroendocrine tumour subtypes suggest tumour type-dependent different pathways in tumour growth control by IGF system components.
胰岛素样生长因子(IGF)及其相应受体和结合蛋白在多种肿瘤的致癌过程中起重要作用,但它们在功能和生物学特性各异的胃肠道胰腺神经内分泌肿瘤中的表达模式仍 largely 未知。
本研究采用逆转录聚合酶链反应(RT-PCR),探寻 IGF 系统各组分:IGF-1 和 IGF-2、IGF 受体 1 和 2(IGF-1R、IGF-2R)、IGF 结合蛋白 1-6(IGFBP1-6)在最常见的胃肠道胰腺神经内分泌肿瘤(胃泌素瘤、胰岛素瘤、类癌综合征相关肿瘤及无功能肿瘤)中的 mRNA 表达模式。
在分析的 37 个肿瘤样本中(9 个胃泌素瘤、10 个胰岛素瘤、9 个类癌综合征相关肿瘤和 9 个无功能肿瘤),所有肿瘤样本均检测到 IGFBP-2,而 IGFBP-1 在这四种肿瘤类型中仅低频率表达(10%-22%)。IGF-2R 主要在胃泌素瘤中表达。在这四种肿瘤类型中,IGF-1R、IGF-2R 和 IGFBP-6 的表达差异显著。此外,还检测到 12 对显著共表达的 IGF 系统组分(IGF-1 <--> IGF-1R、IGF-1 <--> IGF-2R、IGF-1 <--> IGFBP-3、IGF-1 <--> IGFBP-6、IGFBP-3 <--> IGF-1R、IGFBP-6 <--> IGF-1R、IGFBP-1 <--> IGF-2R、IGFBP-3 <--> IGF-2R、IGFBP-5 <--> IGF-2R、IGFBP-3 <--> IGFBP-5、IGFBP-3 <--> IGFBP-6、IGFBP-5 <--> IGFBP-6)。
IGF 系统组分在神经内分泌肿瘤亚型中的表达模式差异表明,IGF 系统组分在肿瘤生长控制中存在肿瘤类型依赖性的不同途径。