胰岛素样生长因子IGF系统与鱼类性腺的研究进展

IGFs系统包含3个配体(IGF-1、IGF-2、IGF-3)、2个受体(IGF-1R、IGF-2R)和6个IGF结合蛋白(IGFBP).生殖和生长是生物体最基本的特征,两者既密切相关又相互区别,胰岛素样生长因子(IGFs)是生长轴和生殖轴相交联的关键因子.最近研究表明:鱼类性腺的发育及成熟伴随着细胞分化和组织生长,传统的生长因子IGF-1、IGF-2和最近发现的IGF-3,对鱼类性腺发挥着重要作用.本文重点介绍鱼类特有的配体IGF-3的结构,鱼类IGFs系统的信号通路及其与鱼类性腺的相关性研究进展.     

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。     

胰岛素样生长因子系统的营养调控

胰岛素样生长因子系统的营养调控邹仕庚王恬（南京农业大学动物科技学院,南京２１００９５）胰岛素样生长因子（ＩＧＦ）因其结构和功能类似胰岛素而得名,ＩＧＦ主要包括ＩＧＦⅠ和ＩＧＦⅡ。体内多种组织都能合成ＩＧＦ,表达ＩＧＦ受体;ＩＧＦ大部分由肝脏合成,...     

胰岛素样生长因子研究进展

胰岛素样生长因子（ＩＧＦ）是一类多功能细胞增殖凋控因子。因其化学结构民胰岛素原类似而得名。ＩＧＦ系统由２个多肽类生长因子、２类受体和至少６种结合蛋白组成。本仅不ＩＧＦ系统成员的分子生物学方面的最新进展及其主要生物学功能作一综述。     

胰岛素样生长因子Ⅰ与生长激素的关系

胰岛素样生长因子Ⅰ与生长激素的关系邹仕庚盛爱武高峰（南京农业大学动物科技学院,２１００９５）１９５７年,Ｓａｌｍａｎ和Ｄａｕｇｈａｄａｙ发现正常大鼠血清能促进３５Ｓ进入培养的软骨细胞,而切除垂体的大鼠血清缺乏对这种硫化过程的促进作用。给切除垂体的大鼠...     

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。     

胰岛素样生长因子与糖尿病神经病变

糖尿病神经病变给糖尿病患者造成严重危害,但其发生机制至今未明。最近研究表明：胰岛素样生长因子（ＩＧＦｓ）对感觉、运动及交感神经元具有支持营养作用;临床糖尿病患者及实验性糖尿病大鼠体内ＩＧＦｓ活性及ＩＧＦｓ ｍＲＮＡ表达水平下降;补充ＩＧＦｓ可减轻糖尿病神经损害程度。上述研究提示ＩＧＦｓ活性下降在糖尿病神经病变的发生中起重要作用。     

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。     

生长激素/胰岛素样生长因子1与阿尔茨海默病

生长激素／胰岛素样生长因子-1（GH／IGF-1）轴的合成、分泌、调节及生物学活性与阿尔茨海默病（AD）有密切关系。生长激素（GH）的合成和分泌受生长激素释放激素（GHRH）正向调节。GH／IGF-1轴活性下降导致一系列生理功能变化。GH／IGF-1缺乏可引起衰老及神经退行性变（AD）而导致认知功能的下降,相应激素的补给可以抑制或逆转这种认知障碍。越来越多的证据表明：GH／IGF-1参与AD型痴呆病理过程,对AD有很好的治疗应用前景。本文就生长激素／胰岛素样生长因子1在AD发病中的机理和药理学研究做一综述。     

团头鲂胰岛素样生长因子-Ⅰ基因克隆与分析

胰岛素样生长因子－Ⅰ（IGF－Ⅰ）是一单链多肽。在脊椎动物中,IGF－Ⅰ通过介导生长激素达到促进生长的作用。为研究鲤科鱼类IGF－Ⅰ的结构功能及在水产养殖中的潜在应用前景,采用逆转录－聚合酶链式反应（RT－PCR）方法,从团头鲂（Megalobrama amblycephala）肝脏的总RNA中扩增出IGF－Ⅰ cDNA。测定了该基因序列,推导其编码的蛋白质序列,克隆的cDNA序列编码包括信号肽和B、C、A、D、E6个区域的161个氨基酸。E区域分析结果表明所克隆的团头鲂IGF－Ⅰ序列属于IGF－ⅠEa-2亚型。     

Twinning propensity and offspring in utero growth covary in rural African women

In humans and other mammals, some females are more likely to experience twin pregnancies than others, but the reasons behind such individual variation are poorly understood. One hypothesis invokes variation in the dynamics of the insulin-like growth factor (IGF) system, which also regulates foetal growth. Using data from a rural African population living in a highly seasonal environment, we test a novel prediction generated by this hypothesis, that maternal twinning status predicts offspring birthweight. We found that among singleton offspring who experience a favourable in utero environment (born January-June), births before and after twins are, respectively, associated with a 134.07 g and 226.41 g increase in birthweight compared with those born to non-twinning mothers. These results were not mediated by maternal anthropometry. This is consistent with a role for the IGF system in individual variation in twinning propensity, a possibility with implications for understanding mechanisms of life-history variation in humans and other vertebrates.     

肝细胞生长因子诱导人肝癌细胞上皮间质化

上皮间质转化（epithelial-mesenchymal transition,EMT）与肿瘤侵袭转移密切相关.虽然肝细胞生长因子（hepatocyte growth factor,HGF）已被证实为肿瘤EMT的主要诱导剂,但是HGF诱导肿瘤EMT发生的分子机制尚不完全清楚.本研究旨在探讨Snail在HGF诱导肝癌细胞上皮间质转化中的作用.用HGF处理肝癌HepG2和Hep3B细胞,显微镜观察细胞形态变化,划痕试验及Transwell试验检测细胞迁移能力,Western印迹检测Met,AKT的磷酸化及蛋白质表达的变化,Western印迹与real-time RT-PCR检测上皮细胞表面标志E-Cadherin和间质细胞表面标志N-Cadherin、Fibronectin的表达变化,以及EMT相关转录因子的表达变化.经HGF处理的HepG2、Hep3B细胞,Met和AKT的磷酸化水平显著增强;相差倒置显微镜下观察细胞形态向间质型细胞形态转化;细胞划痕和Transwell试验检测细胞的迁移能力较对照组显著增强;Real-time RT-PCR和Western印迹实验显示HGF的诱导能上调间质标记蛋白的表达及下调上皮型标志蛋白的表达.进一步发现,HGF能上调转录因子Snail的表达,干扰Snail能逆转HGF对HepG2和Hep 3B细胞EMT发生的诱导作用.由此可见,HGF可能通过诱导Snail的表达促进肝癌细胞EMT的发生.这为阐明肝癌细胞侵袭转移机制,以及肝癌的防治提供新线索.     

Polycomb chromobox 4 enhances migration and pulmonary metastasis of hepatocellular carcinoma cell line MHCC97L

We recently report that the expression of polycomb chromobox 4(Cbx4)is significantly correlated with the overall survival of a great cohort of hepatocellular carcinoma(HCC)patients and it enhances hypoxia-induced vascular endothelial growth factor(VEGF)expression and angiogenesis in HCC cells through enhancing sumoylation of hypoxia inducible factor-1alpha(HIF-1α).Here we continue to investigate the potential effects of Cbx4 on the migration and metastasis of the metastatic HCC cell line MHCC97L.Our results show that Cbx4 overexpression in the cell line increases the in vitro vessel formation of vascular endothelial cells in its SUMO interaction motifs-dependent manner,and promotes the in vitro migration of the cancer cell,which can be effectively abrogated by anti-VEGF antibody.Although Cbx4 expression does not impact the in vitro growth of MHCC97L cells,it still promotes the progression and metastasis of orthotopically transplanted tumors in nude mice.These results further support the role of Cbx4 as a SUMO E3 ligase in the progression and metastasis of HCC.     

Circulating cell-free DNA of methylated insulin-like growth factor-binding protein 7 predicts a poor prognosis in hepatitis B virus-associated hepatocellular carcinoma after hepatectomy

The initiation and progression of hepatocellular carcinoma (HCC) is a multistage process involving a variety of changes at the gene level. Methylation of insulin-like growth factor-binding protein 7 (IGFBP7) plays a crucial role in HCC development. The main purpose of this study was to investigate the relationship between oxidative stress, DNA methyltransferases (DNMTs) expression, and IGFBP7 methylation, and to evaluate the prognostic value of serum IGFBP7 methylation status in patients with HCC after hepatectomy. We enrolled 155 patients with HCC undergoing surgical resection. The IGFBP7 methylation status, DNMTs mRNA levels and malondialdehyde (MDA), xanthine oxidase (XOD), reduced glutathione hormone (GSH), and glutathione-S-transferases (GST) levels were detected. MDA and XOD levels were significantly higher in IGFBP7 methylated group than unmethylated group, while GSH level was lower in methylated group than unmethylated group. The DNMT1 and DNMT3a mRNA levels were higher in IGFBP7 methylated group than unmethylated group. Kaplan–Meier curve analysis revealed that IGFBP7 promoter methylation was significantly correlated with overall survival (OS) (p?IGFBP7 methylation was an independent prognostic predictor for OS (p?=?.000) and early tumour recurrence (ETR) (p?=?.008) in HCC after hepatectomy. Our results indicated that IGFBP7 promoter methylation was associated with oxidative stress and DNMTs expression. Meanwhile, IGFBP7 promoter methylation was associated with OS and ETR, indicating that it might serve as a potentially independent prognostic factor in patients with HCC after hepatectomy.     

A new serum-free method of measuring growth factor activities for human breast cancer cells in culture

Summary Growth of the MCF-7, T47D, and ZR-75-1 human breast cancer cells was established in a serum-free defined medium (MOM-1) composed of a 1∶1 (vol/vol) mixture of Ham's F12 medium and Dulbecco's modified Eagle's medium containing 15 mM HEPES (pH 7.2), 2 mM 1-glutamine, 20 μg/ml glutathione, 10 μg/ml insulin, 10 μg/ml transferrin (Tf), 10 ng/ml selenous acid, 0.3 nM triiodothyronine, 50 μg/ml ethanolamine, 20 ng/ml epidermal, growth factor, 2.0 nM 17β-estradiol, and 1.0 mg/ml bovine serum albumin (BSA). Proliferation in MOM-1 was 50 to 70% of the serum stimulated rate. Deletion of components from MOM-1 gave a medium (Tf-BSA) containing only HEPES, 10 μg/ml Tf, and 200 μg/ml BSA, which sustained MCF-7 and T47D cells in a slowly dividing and mitogen responsive state; ZR-75-1 cells required Tf plus 1.0 mg/ml BSA. In Tf-BSA, insulin and insulin-like growth factor I(IGF-I) were mitogenic with ED₅₀ values of 2 to 3 ng/ml and 30 to 150 pg/ml, respectively, with MCF-7 cells. The T47D cells were responsive to these factors in Tf-BSA but required 10-fold higher concentrations for ED₅₀. At saturating concentrations, insulin and IGF-I promoted 1.5 to 3.5 cell population doublings over controls in 8 d. At≤ng/ml concentrations, epidermal growth factor, insulin-like growth factor II, and basic fibroblast growth factor were mitogenic for human breast cancer cells in Tf-BSA. Mitogen activities in uterus and pituitary extracts were assayed readily in Tf-BSA. This new method offers a convenient means of comparing the potencies of growth-promoting factors on human breast cancer cells without interfering activities known to be present in serum. This work was supported by grants CA-38024 and CA-26617, from the National Cancer Institute, Bethesda, MD, and by American Cancer Society grant BC-255 and grant 2225 from the Council for Tobacco Research, USA, Inc.