Klotho functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). Altered expression and/or activity of growth factor receptor have been implicated in ccRCC development. Although Klotho suppresses a tumor progression through growth factor receptor signaling including insulin-like growth factor-1 receptor (IGF-1R), the role of Klotho acting on IGF-1R in ccRCC and its clinical relevance remains obscure. Here, we show that Klotho is favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. Our data shows the following key findings. First, in tumor tissues, the level of Klotho and IGF-1R expression are low or high, respectively, compared to that of adjacent non-neoplastic parenchyma. Second, the Klotho expression is clearly low in higher grade of ccRCC and is closely associated with clinical outcomes in tumor progression. Third, Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. These results provide compelling evidence supporting that Klotho acting on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC.
Carcinoma, Renal Cell* ; Cell Proliferation ; Prognosis ; Receptor, IGF Type 1

OBJECTIVE: To explore the effect of dihydromyricetin on the expression of miR-98-5p and its mechanism in the development of Herceptin resistance in SKBR3 cells. METHODS: The expression of IGF2 and miR-98-5p and their interaction relationship were analyzed by bioinformatics analysis through TargetScan online databases. SKBR3 cells and drug-resistant SKBR3-R cells were cultured in cell experiments. Xenograft tumor mice were constructed by SKBR3 and SKBR3-R cells. Proteins were detected by western blotting and immunohistochemistry. Transfected cells were constructed by shRNA lentivirus vectors. RT-QPCR was used to detect RNA. Cell proliferation was detected by MTS method. Cell jnvasion was detected by Transwell assay. Luciferase reporting assays were used to verify RNA interactions. IGF-1R/HER2 heterodimer was determined by immunocoprecipitation. RESULTS: The expression of IGF2, p-IGF1R, p-Akt and p-S6K in SKBR3-R cells were significantly higher than those in SKBR3 cells, while the expression of PTEN protein was lower in SKBR3-R cells (P < 0.05). IGF1R/HER2 heterodimer in SKBR3-R cells was significantly increased (P < 0.01).The expression of IGF2 and invasion ability were significantly reduced while transfected with miR-98-5p in SKBR3-R cells (P < 0.05), but the IGF2 mRNA were no difference in both cells (P > 0.05). The expression of miR-98-5p was up-regulated and IGF2 was decreased in drug-resistant xenograft tumor mice after feeding with dihydromyricetin, and the tumor became more sensitivity to Herceptin (P < 0.05). CONCLUSION Dihydromyricetin could induce the expression of miR-98-5p, which binds to IGF2 mRNA to reduce IGF2 expression, inhibit the IGF-1R/HER2 formation, thereby reversing cell resistance to Herceptin in SKBR3-R cells.
Animals ; Cell Line, Tumor ; Flavonols/pharmacology* ; Humans ; Mice ; MicroRNAs/metabolism* ; Receptor, IGF Type 1 ; Trastuzumab

Animals ; Apoptosis ; Cell Line, Tumor ; Down-Regulation ; Melanoma, Experimental ; pathology ; virology ; Mice ; Receptor, IGF Type 1 ; physiology ; Sendai virus ; pathogenicity

OBJECTIVETo study the association between single nucleotide polymorphism (SNP) of insulin-like growth factor I receptor (IGF-IR) gene and idiopathic short stature (ISS).

METHODSA total of 804 children with ISS and 575 normal controls were recruited from 2008 to 2011. IGF-IR gene SNP was genotyped using the Snapshot Multiplex System.

RESULTSThe distribution frequency of genotype rs1976667 showed no significant difference between the ISS and the control groups, while that of the allele A of rs1976667 was significantly higher in the ISS group than in the control group (P<0.01).

CONCLUSIONSThe allele A at rs1976667 SNP of IGF-IR gene is a risk factor for ISS.

Adolescent ; Child ; Child, Preschool ; Female ; Growth Disorders ; genetics ; Humans ; Male ; Polymorphism, Single Nucleotide ; Receptor, IGF Type 1 ; genetics

Patients with acromegaly have high incidence of benign or malignant neoplasia than general population and many investigators suggest the stimulatory effect of GH and IGF-1 on mesenchymal cells. Both normal thyroid tissue and thyroid cancer cells express IGF-1 receptor and thyroid cancer cells have more than 3 times. We present a case of acromegaly in patient with mixed papillary-follicular thyroid carcinoma, suggesting the possible carcinogenic role of GH and IGF-1.
Acromegaly* ; Humans ; Incidence ; Insulin-Like Growth Factor I ; Receptor, IGF Type 1 ; Research Personnel ; Thyroid Gland* ; Thyroid Neoplasms*

Nicotine is one of the major components of cigafette smoking which causes various systemic and local diseases to human body. Mitrogenic effects of nicotine to systemic disease are interesting factors in the results of cellular proliferation especially to vascular and pulminary tissus or cells. The study of local effects concerns with destruction of tissue and delayed healing rate after various surgicla treatment. Platelet-Derived Growth factor(PDGF) and Insulin-like growth factor(IGF) are known as major mitogens to human PDL cells. The purpose of this studywas to investgate the mitogenic effects of nicotine to human PDL cells. We studied the expression of PDGF-alpha receptor, PDGF-betareceptor, and IGF-1 receptor mRNA form the nicotine treated human PDL cells by northern analysis. The experimental groups were divided into different serum(1%, 10%) and nicotine(100ng/ml, 1000ng/ml) condentrations and each group was studied by time course. The results of this study showed upregulation of PDGF-alpha, beta receptor and IGF-1 receptor mRNA at 100ng/ml nicotine concentration and 10% serum group to the time course. These results suggest that physiologically attainable nicotine concentrations may stimulate mitogenic gene synthesis to human PDL cells in vitro.
Cell Proliferation ; Human Body ; Humans* ; Mitogens ; Nicotine* ; Receptor, IGF Type 1 ; RNA, Messenger ; Smoke ; Smoking ; Up-Regulation

As a hormone with a number of biological effects, insulin not only displays the function of classic metabolic regulation, but also can regulate cell proliferation and differentiation, and ensure growth and development of embryos and young individuals. In vitro insulin can stimulate cell proliferation and differentiation. Insulin is also an important growth regulator in vivo, which has been proved in more and more studies. The role of insulin at the cellular level is triggered by the binding of insulin to its receptor located in the cell surface. However, insulin at the higher concentration can also been triggered by insulin-like growth factor-1 (IGF-1) receptor. Its role varies in different cell lines. Insulin receptor and insulin-like growth factor receptor-1 are widely expressed in human MDS and AML cell membranes. Recently, many studies related to the relationship between hyperinsulinemia and cancer have been reported. In this review the role and its possible mechanism in promoting human leukemia cell proliferation and inhibiting human leukemia cell proliferation are summarized. Furthermore, the potential application prospect of insulin analogues also will be described.
Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Humans ; Insulin ; pharmacology ; Leukemia ; metabolism ; pathology ; Receptor, IGF Type 1 ; metabolism ; Receptor, Insulin ; metabolism

This study was aimed to explore the effects of insulin on expression of insulin receptor (IR) and insulin-like growth factor-I receptor (IGF-IR) in Reh cells and promoting effect on proliferation of Reh cells. The proliferation of Reh cells were evaluated by CCK-8 assay. The expression levels of IR and IGF-IR mRNA in Reh cells at different times were detected by real-time quantitative polymerase chain reaction. The results showed that insulin promoted the proliferation of Reh cells in dose- and time-dependent manners. Compared with the control group, insulin promoted the proliferation of Reh cells obviously (P < 0.05). When Reh cells were treated with insulin 10(-9) mol/L for 24, 48 and 72 h, the relative quantity of IR expression (2(-ΔCt1)/2(-ΔCt2)) was 2.2520 ± 0.7431, 1.9956 ± 0.9692 and 3.9766 ± 1.3189, respectively, the relative quantity of IGF-IR expression was 1.0803 ± 0.2238, 1.6026 ± 0.6158 and 3.1013 ± 0.1008, respectively, compared with the control group. The expression levels of IR and IGF-IR mRNA in Reh cells treated with insulin were obviously increased compared with the control group. It is concluded that insulin promotes the proliferation of Reh cells. The high expression levels of IR and IGF-IR may closely related with the growth of leukemia cells.
Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Insulin ; pharmacology ; Leukemia, Lymphoid ; metabolism ; pathology ; Receptor, IGF Type 1 ; metabolism ; Receptor, Insulin ; metabolism

Mesenchymal tumors including hemangiopericytomas, hepatocellular tumors, adrenal carcinomas, and a variety of other large tumors have been reported to produce excessive amounts of insulin-like growth factor (IGF) type II precursor, which binds weakly to insulin receptors and strongly to IGF-I receptors, leading to insulin like actions. In addition to increased IGF-II production, IGF-II bioavailability is increased due to complex alterations in circulating binding proteins. The authors of this article diagnosed non-islet cell tumor hypoglycemia from an 81-year-old male patient suffering from repetitive fasting hypoglycemia while he has not received any treatment for pulmonary hemangiopericytoma diagnosed in the past. Moreover, this topic is getting reported as the authors have experienced a significant improvement of catamnesis by a treatment with glucocorticoid.
Aged, 80 and over ; Biological Availability ; Carrier Proteins ; Hemangiopericytoma ; Humans ; Hypoglycemia* ; Insulin ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Male ; Receptor, IGF Type 1 ; Receptor, Insulin

We present three cases of malignant solitary fibrous tumors of the pleura (SFTP) that produced recurrent hypoglycemia. Removal of the tumors produced normoglycemia. The tumors were well circumscribed and lobulated, and consisted of firm masses weighing 1,150 g to 1,450 g with the greatest diameter of 15 to 20 cm. The tumors were composed of spindle cells in fascicles or in a haphazard arrangement and were highly cellular and mitotically active (3-8 mitoses/10 high-power fields), showing histologically malignant features. Ultrastructurally, fibroblastic features of the tumor cells were present. Insulin-like growth factors (IGF) have been implicated in the presentation of hypoglycemia. The serum insulin and C-peptide levels were not elevated. Serum IGF-I levels were also low with values of 97.4, 157.1 and 51.9 ng/mL (ref. 125-317 ng/mL), respectively. However, tumor cells were strongly positive for IGF-I receptor on immunohistochemical analysis. It is tempting to speculate that IGF-I contributes to the hypoglycemia, even though the circulating levels were low.
Aged ; Blood Glucose ; Coin Lesion, Pulmonary/chemistry/*complications/pathology ; Female ; Human ; Hypoglycemia/*etiology ; Immunohistochemistry ; Male ; Middle Age ; Pleural Neoplasms/chemistry/*complications/pathology ; Receptor, IGF Type 1/*analysis ; Recurrence