IGFs与消化系统肿瘤及妇科肿瘤的研究进展

胰岛素样生长因子系统(Insulin-like growth factor system,IGFs)包括胰岛素样生长因子(Insulin-like growth factor,IGF)、胰岛素样生长因子受体(Insulin-like growth fact receptor,IGFR)以及胰岛素样生长因子结合蛋白(Insulin-like growth fact binding proteins,IGFBPs)。IGFs在上皮生长、抗凋亡及促有丝分裂中起着重要的作用。大量研究表明IGFs在不同恶性肿瘤细胞株、患者血清及其肿瘤组织均有不同程度的表达,与肿瘤的发生、发展及预后密切相关。本文就目前IGFs与消化系统肿瘤与妇科肿瘤的研究进展进行综述,为早期诊断、治疗及预测恶性肿瘤预后提供帮助。     

胰岛素样生长因子结合蛋白2与消化系统肿瘤的关系

胰岛素样生长因子结合蛋白2(Insulin-like growth factor binding-protein 2,IGFBP-2)是属于胰岛素样生长因子超家族中的一员,可以通过胰岛素样生长因子(Insulin-like growth factor,IGF)依赖和非依赖机制,在肿瘤的生长、增殖、转移、侵袭过程中发挥作用,还可以作为评价恶性肿瘤复发和预后的指标。本文详述了IGFBP-2的基因结构、蛋白结构、功能、信号转导途径及其与消化系统恶性肿瘤关系的研究进展,以期为消化系统恶性肿瘤的治疗提供新思路。     

牙鲆变态中IGF-I基因表达及甲状腺激素对其的调节作用

胰岛素样生长因子(Insulin-like growth factors,IGFs)是一类具有胰岛素样代谢和促有丝分裂功能的蛋白质,参与脊椎动物的胚胎发育、生长和生殖。IGF系统包括两个配体(IGF-Ⅰ、IGF-Ⅱ)、IGF受体(IGF-I receptor,IGF-I R;IGF-II receptor,IGF-ⅡR)以及IGF结合蛋白(IGF binding     

胰岛素样生长因子家族与肺癌

胰岛素样生长因子(IGFs)家族与多种肿瘤的发生发展关系密切。本文综述了IGFs和胰岛素样生长因子受体(IGFRs)以及胰岛素样生长因子结合蛋白(IGFBPs)在肺癌发生发展、增殖、侵袭、转移和凋亡中所起的作用及其作用机制。为肺癌的预防、治疗、预后提供新的思路。     

卵巢中的胰岛素样生长因子系统

本文详细阐述了胰岛素样生长因子（IGFs)系统各个成员的结构及其在卵巢中的表达和作用机制。IGFs是这一系统的中间环节,与IGFs受体作用刺激卵巢细胞中类固醇激素的生产和DNA合成,能够介导和扩大促性腺激素对卵巢功能的作用。IGFs与胰岛素样生长因子结合蛋白（IGFBPs)发生高亲和性结合,卵巢中自由的IGFs的水平受IGFBPs的调节。而IGFBPs蛋白酶能够降低IGFBPs和IGFs的亲和性,从而参与调节IGFs在卵巢中的作用。深入的研究这一系统,对于进一步了解卵巢卵泡生长发育、分化以及闭锁,卵泡细胞的增殖和凋亡的内在机制,以及提高动物的繁殖力有重要意义。     

莲草直胸跳甲胰岛素样生长因子系统相关基因IGFALS和IMP3的表达模式

莲草直胸跳甲Agasicles hygrophila是恶性入侵杂草空心莲子草Alternanthera philoxeroides的专食性天敌。为阐明该跳甲生殖调控的分子机制,筛选其卵巢转录组数据得到3个胰岛素样生长因子系统相关基因,分别为胰岛素样生长因子酸不稳定亚基(IGFALS)和其亚型X1 (IGFALS X1)以及胰岛素样生长因子II mRNA结合蛋白3 (IMP3),利用半定量PCR方法检测3个基因在雌成虫不同发育时期的表达模式,并通过荧光定量PCR技术检测其在不同组织及不同发育时期的表达水平。结果显示,筛选到的IGFALS、IGFALS X1和IMP3基因在莲草直胸跳甲蛹期和成虫期均有表达,且3个基因在蛹期和成虫期均为全身性表达,IGFALS和IMP3 mRNA在成虫卵巢组织中表达量显著高于其他组织,峰值分别出现在成虫羽化后第5天和第1天,较蛹期第1天分别增加了3.56和3.81倍,因此推测IGFALS和IMP3基因在莲草直胸跳甲卵子发生过程中发挥重要的调控作用。     

猪背最长肌中胰岛素样生长因子(IGFs)系统基因的发育表达模式

采用荧光定量PCR技术检测了长白猪和梅山猪的背最长肌组织中胰岛素样生长因子1和2(IGF-1和-2)、胰岛素样生长因子1受体和2受体(IGF-1R和-2R)、胰岛素样生长因子结合蛋白3和5(IGFBP-3和-5)基因mRNA丰度在初生(0月龄)、1、2、3、4和5月龄间的表达变化并分析品种间和不同月龄间基因表达的差异及其对肌肉生长发育的影响。结果表明: 两猪种出生后IGF-1 mRNA表达量均表现为逐渐上调, 而IGF-2则恰好相反, 表现为逐渐下调。这与IGF-2主要在胚胎期发挥作用, 而IGF-1则主要在动物个体出生后才发挥促进细胞增殖和个体发育功能的特点相符。IGFRs mRNA与IGFs mRNA 表达的发育性变化模式并不相似, 提示背最长肌组织中IGFRs mRNA 的表达可能没有受到组织局部产生的IGFs调节。长白猪的IGF-1R、IGF-2R 和IGFBP-3 mRNA表达量均在2月龄时达到最高峰, 提示2月龄可能是长白猪IGFs系统发挥作用最为明显的生长发育阶段。以上结果初步揭示猪生长发育过程中胰岛素样生长因子系统基因表达的发育性变化模式和品种差异, 为深入研究胰岛素样生长因子系统基因的相互调控机制提供了基础数据。     

无脊椎动物胰岛素样蛋白(Insulin-like/related peptides)研究进展——以昆虫为例

胰岛素样蛋白(Insulin-like/related peptides,ILPs)是无脊椎动物中胰岛素的同源基因。以昆虫为例,概述了ILPs的结构、表达以及相关通路特别是胰岛素信号通路(Insulin signaling pathway),并总结了其在调控机体生长、发育、新陈代谢、繁殖和免疫等生命过程中的作用。     

胰岛素样生长因子与哺乳动物的胚胎发育

综述了胰岛素样生长因子(IGFs)在胚胎发育过程中的表达特点和对胚胎发育的作用。许多研究表明,IGFs、IGF受体、IGF结合蛋白(IGFBPs)在不同发育阶段的胚胎中具有不同的表达特点,并具有组织特异性。不论是母体来源的、胎儿自身产生的、还是外源性的IGFs都能促进细胞分化和增殖,对胚胎发育有重要作用。     

胰岛素样生长因子2研究进展

胰岛素样生长因子2在胎儿生长发育、肿瘤细胞增殖、肌肉生长等方面具有重要的调控作用。本文综述了胰岛素样生长因子2基因结构、基因组印迹和作为影响肌肉重量数量性状基因座的研究进展。Abstract: Insulin-like growth factors play an important role in fetal growth and development, tumour cell proliferation and muscle growth. This review is focused on the insulin-like growth factor 2 gene structures, and their imprintings in mammalian genomes. In addition, we also discussed that IGF2 is the major paternally expressed candidate gene affecting muscle mass.     

Insulin-like growth factor binding proteins and mammary gland development

Mammary gland development is dependent upon insulin-like growth factors (IGFs) as survival factors. The actions of the IGFs are modulated by a family of IGF-binding proteins (IGFBP1-6). Expression of the IGFBPs is both time-dependent and cell-specific during both the developmental phases and the involution of the mammary gland. Although studied extensively in vitro, understanding the roles of IGFBPs in vivo has been difficult, largely due to the fact that IGFBP knock-out mice have no dramatic phenotypes. This review examines the evidence from in vitro studies and the attempts to examine in vivo actions utilising models with IGFBP deficiency or over-expression. In vitro studies demonstrate that IGFBPs can act by inhibition of the survival effects of IGFs, as well as by enhancing the effects of IGFs. Because the IGFBPs are found associated with the extracellular matrix, a role for IGFBPs as a reservoir of IGFs or, alternatively as a potential barrier to IGFs, thereby restricting their entry into particular tissues or cellular compartments was postulated. We also provide evidence with respect to the IGF-independent actions of the IGFBPs which include receptors, nuclear localization, and interaction with the extracellular matrix and cell surface proteins including integrins. We believe that recent findings place some of the IGFBPs in a larger family of extracellular proteins, the secreted cysteine-rich protein (CCN) family, which have similar structural domains (involved in binding to IGFs, extracellular matrix and integrins) and are heavily implicated in tissue re-modeling and morphogenesis.     

The interaction of Insulin-like Growth Factors (IGFs) with Insulin-like Growth Factor Binding Proteins (IGFBPs): a review

Summary The interactions between insulin-like growth factor binding proteins (IGFBPs) and insulin-like growth factors (IGFs) are important in regulating the availability of IGFs to the type 1 IGF receptor (IGF1R) but there is still a lack of information regarding the mechanism of IGF binding by IGFBPs. While many studies have defined general regions of the IGFBPs that interact with IGFs, only recently have specific IGF binding residues been described. This review will outline the structural evidence describing residues of both the IGFBPs and IGFs involved in the IGFBP·IGF interaction.     

Involvement of growth hormone (GH) and insulin-like growth factor (IGF) system in ovarian folliculogenesis

During the last decade, involvement of growth hormone (GH), insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in ovarian folliculogenesis has been extensively studied. This review provides an update on the GH, IGF system and their role in ovarian follicular development. In vitro studies and knockout experiments demonstrated an important role of GH in preantral follicle growth and differentiation through their binding with GH receptors, which are located both in the oocyte and follicular somatic tissues. Furthermore, GH stimulates the development of small antral follicles to gonadotrophin-dependent stages, as well as maturation of oocytes. With regard to the IGF system, IGF-I has no effects on primordial follicle development, but both IGF-I and IGF-II stimulate growth of secondary follicles. Depending on the species studies and method used, these proteins have been detected in oocytes and/or somatic cells. In antral follicles, these IGFs stimulate granulosa cell proliferation and steroidogenesis in most mammals. The bioavailability of IGFs is regulated by a family of intrafollicular expressed IGF binding proteins (IGFBPs). Facilitation of IGF can be increased through the activity of specific IGFBP proteases, which degrade the IGF/IGFBP complex, resulting in the production of IGFBP fragments and release of attached IGF.     

The Insulin-like Growth Factor System and Its Biological Actions in Fish

The insulin-like growth factor (IGF) system plays an importantrole in controlling animal development and growth. There arethree components to the IGF system: ligands (IGF-I and IGF-II),receptors (type I and type II IGF receptors) and IGF-bindingproteins (IGFBPs). These members of the IGF system are expresseddifferentially and their expression patterns implicate themin critical developmental events. Even though IGFs have beenproven essential for normal fetal growth through experimentsusing IGF "knock-out" mice, the precise role of each memberof the IGF system is not fully understood. Recent studies suggestthat the IGF system has been highly conserved in teleost fish.This paper provides an overview of what is currently known aboutthe IGF system in teleost fish. Several aspects of the IGF systemare discussed, including the structural and functional aspectsof fish IGFs, the fish IGF receptors and IGFBPs. The biologicalactions of fish IGFs are described in reference to their rolesin growth, development, reproduction and osmoregulation. Finally,some of the unique advantages of using teleost fish as experimentalmodels for defining the developmental role of the IGF systemand the underlying molecular mechanisms are discussed     

Insulin-like growth factors as mediators of functional plasticity in the adult brain.

Insulin-like growth factors (IGFs) are present in the brain throughout life. While their role as modulators of brain growth and differentiation during development is becoming apparent, their possible involvement in adult brain function is less known. Nevertheless, accumulating evidence indicates a role for IGFs in brain plasticity processes. Specifically, IGFs modulate synaptic efficacy by regulating synapse formation, neurotransmitter release and neuronal excitability. IGFs also provide constant trophic support to target cells in the brain and in this way maintain appropriate neuronal function. Pathological dearrangement of this trophic input may lead to brain disease. Molecular targets of the IGFs in the adult brain may include pre- and post-synaptic proteins involved in synaptic contacts, membrane channels, neurite-guiding molecules, extracellular matrix components and glial-derived intercellular messengers. Future studies on the role of IGFs in the adult brain may help unravel the relationship between neuronal plasticity and brain disease.     

The interaction of Insulin-like Growth Factors (IGFs) with Insulin-like Growth Factor Binding Proteins (IGFBPs): a review

The interactions between insulin-like growth factor bindingproteins (IGFBPs) and insulin-like growth factors (IGFs)are important in regulating the availability of IGFs to thetype 1 IGF receptor (IGF1R) but there is still a lack ofinformation regarding the mechanism of IGF binding byIGFBPs. While many studies have defined general regions ofthe IGFBPs that interact with IGFs, only recently havespecific IGF binding residues been described. This reviewwill outline the structural evidence describing residues ofboth the IGFBPs and IGFs involved in the IGFBP-IGFinteraction.     

胰岛素样生长因子结合蛋白研究进展

胰岛素样生长因子结合蛋白(IGFBPs)是一组能够和胰岛素样生长因子(IGF)以高亲和力结合的可溶性蛋白,它们不仅携带IGF,延长IGF的半衰期,而且还调控IGF的生物活性, 影响IGF的分布.在不同的实验条件下,IGFBPs能够增强或抑制IGF的活性.另外,又发现IGFBPs有独立于IGF之外的内在的生物活性.简单介绍一下近年来IGFBPs在分子结构、基因表达、翻译后的修饰及生物功能等方面的研究.     

High-yield bacterial expression and structural characterization of recombinant human insulin-like growth factor binding protein-2

The diverse biological activities of the insulin-like growth factors (IGF-1 and IGF-2) are mediated by the IGF-1 receptor (IGF-1R). These actions are modulated by a family of six IGF-binding proteins (IGFBP-1-6; 22-31 kDa) that via high affinity binding to the IGFs (K_D ∼ 300-700 pM) both protect the IGFs in the circulation and attenuate IGF action by blocking their receptor access. In recent years, IGFBPs have been implicated in a variety of cancers. However, the structural basis of their interaction with IGFs and/or other proteins is not completely understood. A critical challenge in the structural characterization of full-length IGFBPs has been the difficulty in expressing these proteins at levels suitable for NMR/X-ray crystallography analysis. Here we describe the high-yield expression of full-length recombinant human IGFBP-2 (rhIGFBP-2) in Escherichia coli. Using a single step purification protocol, rhIGFBP-2 was obtained with >95% purity and structurally characterized using NMR spectroscopy. The protein was found to exist as a monomer at the high concentrations required for structural studies and to exist in a single conformation exhibiting a unique intra-molecular disulfide-bonding pattern. The protein retained full biologic activity. This study represents the first high-yield expression of wild-type recombinant human IGFBP-2 in E. coli and first structural characterization of a full-length IGFBP.     

The insulin-like growth factors and their binding proteins

1. This review provides a brief overview of the structure of the insulin-like growth factors (IGFs or somatomedins), their mRNA and genes; the regulation and sites of production of these peptides; their binding and actions in target tissues; and the structure and biological role of their binding proteins. 2. Molecular cloning techniques have allowed the prediction of precursor forms of IGF-I and IGF-II, have provided tools to study the regulation of the synthesis and translation of IGF mRNAs, and have recently yielded the primary sequence of the IGF-I receptor, supplementing other rapidly-accumulating structural data. 3. Several of the IGF binding proteins have also been purified, and initial structural studies performed. 4. The increased knowledge of the structures of the IGFs, their receptors and binding proteins should now permit rapid progress in understanding the physiology and functions of these proteins.     

Insulin-like growth factor-binding protein-5 (IGFBP-5): a critical member of the IGF axis

The six members of the insulin-like growth factor-binding protein family (IGFBP-1-6) are important components of the IGF (insulin-like growth factor) axis. In this capacity, they serve to regulate the activity of both IGF-I and -II polypeptide growth factors. The IGFBPs are able to enhance or inhibit the activity of IGFs in a cell- and tissue-specific manner. One of these proteins, IGFBP-5, also has an important role in controlling cell survival, differentiation and apoptosis. In this review, we report on the structural and functional features of the protein which are important for these effects. We also examine the regulation of IGFBP-5 expression and comment on its potential role in tumour biology, with special reference to work with breast cancer cells.