Regulatory effects of biophysical strain on rat TMJ discs

Recent studies have revealed that dynamic biomechanical forces can exert antiinflammatory and antiproteolytic effects on fibrocartitage. Whether the effects of mechanical strain also involve stimulation of the insulin-like growth factor (IGF) system and, therefore, of growth and repair of fibrocartilage has yet to be determined. The objective of this in vitro study was to determine if continuous biophysical strain regulates the gene expression of IGF1, IGF2, IGF1 receptor (IGF1R), insulin receptor substrate (IRS1), and IGF-binding proteins (IGFBP) 3 and 5 in cells from the fibrocartilaginous disc of the temporomandibular joint (TMJ). Rat TMJ disc cells were subjected to continuous biophysical strain (3% and 20%) for 4 and 24 h. Subsequently, RNA was extracted and real-time PCR was performed using an iCycler iQ detection system to analyze the gene expression of the IGF system. The gene expression of IGF1, IGF2, IGF1R, IRS1, IGFBP3, and IGFBP5 was significantly (p < 0.05) inhibited when cells were subjected to continuous biophysical strain, as compared to control at both time points. High strain induced a stronger inhibition of these molecules as compared to strain of Low magnitude. In conclusion, continuous biophysical strain seems to downregulate the expression of the IGF system and may, therefore, reduce the potential of fibrocartilage for growth and repair.     

Candidate genes associated with ageing and life expectancy in the Jerusalem longitudinal study

In an exploratory study, 11 common polymorphisms were examined for contributing to longevity including: apolipoprotein E (apoE), methylenetetrahydrofolate reductase (MTHFR), cathepsin D (CAD), superoxide dismutase 2 (SOD2), angiotensinogen (AGT) and insulin-like growth factor 2 (IGF2), Leiden factor 7, p53 oncogene, dopamine D4 receptor (DRD4) and the serotonin transporter (SERT). Genotype and allele frequencies of these genes were compared in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity to a group of 441 younger subjects (22 years). Nominally significant results provide suggestive evidence in the Ashkenazi group that apoE, MHTFR, SOD2, IGF2 ApaI, and factor VII are risk factors for a single outcome, survival to 75. Overall, the more genetically homogenous Ashkenazi ethnic group showed evidence for association in five genes examined suggesting that future studies in this population would gainfully focus on this ethnic group.     

Genomic imprinting and its relevance to genetic diseases

Summary Genomic imprinting is a biological phenomenon determined by an evolutionally acquired, underlying system that may control harmonious development and growth in mammals. It is also relevant to some genetic disorders in man. In this article, lines of biological evidence of imprinting, characteristics of the mouse and human imprinted genes, and findings and mechanisms on the occurrence of several human imprinting disorders are reviewed.     

Messenger RNA encoding the insulin-like growth factors and their binding proteins, in women with fibroids, pretreated with luteinizing hormone-releasing hormone agonists

The primary objective of this study was to suggest a possiblemechanism of action of luteinizing hormone-releasing hormoneagonist (LHRHa) on fibroids. This was performed by investigatinginsulin-like growth factor (IGF)-I, IGF-II and IGF binding protein(IGFBP)-1, -2 and -3 mRNA expression in uterine fibroids fromwomen rendered hypo-oestrogenic by LHRHa, using Northern blotanalysis. Nine women with fibroids, who were rendered hypo-oestrogenicfrom at least 4 months pretreatment with LHRHa therapy priorto undergoing myomectomy were investigated. Our results showedthat IGF-I, IGF-II, IGFBP-2 and -3 mRNAs were expressed in uterinefibroids, and that IGFBP-1 mRNA or protein was not detectedin fibroids. Western ligand blotting showed the presence ofIGFBP-2 and -3 proteins, and when compared with a group of womenwith fibroids not treated with LHRHa (B.J.Vollenhoven et al.,1993, J. Clin. Endocrinol Metab., 76, 1106–1110) we foundthat there was no difference in the relative abundance for eachof the factors between the two groups of women. Therefore, LHRHaact to decrease fibroid size via induction of a hypo-oestrogenicstate rather than by changes in the IGFs and their IGFBPs.     

Beta-catenin abnormalities and associated insulin-like growth factor overexpression are important in phyllodes tumours and fibroadenomas of the breast

The aim of this study was to assess the expression of IGF-I and IGF-II in phyllodes tumours and fibroadenomas and to see if there is any correlation between nuclear beta-catenin expression and IGF-I and IGF-II expression in these tumours. In a previous study, it has been shown that Wnt signalling is important in the pathogenesis of phyllodes tumours of the breast. Epithelial Wnt5a overexpression and stromal Wnt2 overexpression were associated with abnormal, nuclear localization of beta-catenin in the stromal cells of these tumours. However, not all tumours with beta-catenin accumulation showed Wnt overexpression. One other possible cause of beta-catenin accumulation is overexpression of insulin-like growth factors (IGFs), as both IGF-I and IGF-II have been shown to stabilize beta-catenin. In this study, 30 fibroadenomas of the breast were assessed for beta-catenin expression using immunohistochemistry and the results were compared with previous data from 119 phyllodes tumours. In situ hybridization was used to assess IGF-I and IGF-II expression in 23 phyllodes tumours and 16 fibroadenomas. Nineteen phyllodes tumours (83%) showed widespread overexpression of IGF-II and 5/23 (22%) showed widespread overexpression of IGF-I. IGF-I expression correlated with nuclear beta-catenin staining in phyllodes tumours. Malignant phyllodes tumours showed no or little IGF-I expression. There was a degree of nuclear beta-catenin expression in the stroma (weak in 33%, moderate in 27%, and strong in 40%) in all fibroadenomas and nuclear beta-catenin staining correlated with IGF-I overexpression. Extensive IGF-II overexpression was also found in the majority of fibroadenomas (12/16). These results support the hypothesis that IGF-I and IGF-II overexpression may be important in the pathogenesis of fibroepithelial neoplasms of the breast and that IGF-I overexpression is likely to be contributing to the nuclear beta-catenin localization observed in the tumours.     

Paracrine/autocrine regulation of breast cancer by the insulin-like growth factors

Local environmental signals regulate the growth and development of both normal and malignant breast epithelium. Members of the insulin-like growth factor (IGF) family likely influence both of these processes. The localization of IGF2 to stroma specifically surrounding malignant breast epithelium indicates that this growth factor may play a critical role in the genesis or maintenance of this transformed phenotype. Recent studies have sought to understand the mechanism by which IGF2 expressing fibroblasts are localized to the periphery of malignant breast cancer cells. In addition, the consequences of the expression of IGF-signaling components likely expand beyond their direct effects on mitogenesis. Indirect effects predominantly associated with the IGF2 receptor could also influence the invasive potential of breast tumor cells.     

抑癌基因PTEN和胰岛素样生长因子-1受体在子宫内膜癌中的表达及临床意义

目的研究抑癌基因PTEN和胰岛素样生长因子1受体(IGF1R)与子宫内膜癌临床及病理特征的关系。方法应用免疫组织化学方法(SP法)检测45例子宫内膜癌组织中PTEN基因和胰岛素样生长因子1受体的表达。结果45例子宫内膜癌组织中,PTEN阳性表达率为28.89%;Ⅰ期患者和Ⅱ～Ⅲ期患者阳性表达率分别为44.00%和10.00%(P<0.05);在高、中、低分化子宫内膜癌中的阳性表达率分别为60.00%、15.00%和10.00%(P<0.05);无、有淋巴结转移者的阳性表达率分别为38.71%和7.14%(P<0.05);IGF1R阳性表达率为86.67%。结论PTEN基因抑制子宫内膜癌的生长、浸润及淋巴结转移;IGF1R在子宫内膜癌的发生中发挥着重要作用。     

IGF、细胞凋亡与涎腺疾病的研究进展

涎腺疾病为口腔科常见病及多发病,它危害人类健康,影响人类生存质量.目前随着对涎腺疾病研究的深入,有关IGF、细胞凋亡与涎腺疾病之间关系的研究,越来越受到人们的重视.本文总结IGF、细胞凋亡与涎腺疾病之间的关系如下.