PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells

Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.

Análisis de asociación de los genes receptor de rianodina (RYR-1) e insulin-like growth factor-2 (IGF-2) con caracteres productivos en una población porcina de tipo comercial en el estado de Nuevo León, México

Tesis (Maestría en Ciencias Veterinarias) U.A.N.L., 2006.

Modulation of Endothelin-1 and Insulin-like Growth Factor Type 1-induced Signaling by Curcumin in A-10 Vascular Smooth Muscle Cells

Les maladies cardio-vasculaires (MCV), telles que l’hypertension et l’athérosclérose, s’accompagnent de modifications structurales et fonctionnelles au niveau vasculaire. Un fonctionnement aberrant de la migration, l’hypertrophie et la prolifération des cellules musculaires lisses vasculaires (CMLV) sont des évènements cellulaires à l’origine de ces changements. L’endothéline-1 (ET-1) contribue à la pathogénèse des anomalies vasculaires, notamment via l’activation des protéines MAPK et PI3-K/PKB, des composantes clés impliquées dans les voies prolifératives et de croissance cellulaires. Il a été suggéré que le stress oxydant jouerait un rôle intermédiaire dans les effets pathophysiologiques vasculaires de l’ET-1. En conséquence, une modulation de la signalisation induite par l’ET-1 peut servir comme éventuelle stratégie thérapeutique contre le développement des MCV. Il apparaît de nos jours un regain d’intérêt dans l’utilisation des agents phyto-chimiques pour traiter plusieurs maladies. La curcumine, constituant essentiel de l’épice curcuma, est dotée de plusieurs propriétés biologiques parmi lesquelles des propriétés anti-oxydantes, anti-prolifératrices et cardio-protectrices. Cependant, les mécanismes moléculaires de son effet cardio-protecteur demeurent obscurs. Dans cette optique, l’objectif de cette étude a été d’examiner l’efficacité de la curcumine à inhiber la signalisation induite par l’ET-1 dans les CMLV. La curcumine a inhibé la phosphorylation des protéines IGF-1R, PKB, c-Raf et ERK1/2, induite par l’ET-1 et l’IGF-1. De plus, la curcumine a inhibé l’expression du facteur de transcription Egr-1 induite par l’ET-1 et l’IGF-1, dans les CMLV. Ces résultats suggèrent que la capacité de la curcumine à atténuer ces voies de signalisation serait un mécanisme d’action potentiel de ses effets protecteurs au niveau cardiovasculaire.

Relationships between the plasma concentrations of insulin-like growth factor-I in dairy cows and their fertility and milk yield

The relationships between insulin-like growth factor-I (IGF-I) and the fertility and milk yield of Holstein-Friesian dairy cows were investigated. The concentration of IGF-I in blood was measured weekly from one week before to 12 weeks after calving in 177 multiparous cows and at four times during this period in 142 primiparous cows; the concentration of IGF-I in milk was measured in 50 of the multiparous cows. The plasma concentrations of IGF-I were higher in the primiparous than in the multiparous animals. in the primiparous cows, high concentrations of IGF-I before calving were associated with longer calving to conception intervals. Conversely, in the multiparous cows low concentrations of IGF-I before and after calving were associated with a failure to conceive, despite repeated services. Multiparous cows with IGF-I concentrations of greater than 25 ng/ml in the week after calving were 11 times more likely to conceive to first service than those with lower concentrations. Concentrations of IGF-I greater than 50 ng/ml at first service increased the likelihood of conception five-fold. Cows with higher peak milk yields had lower plasma concentrations of IGF-I and took longer to return to ovarian cyclicity. The negative relationship between milk yield and return to cyclicity was stronger in the multiparous cows (P<0(.)002) than in the primiparous cows (P<0(.)04). The concentrations of IGF-I in milk followed a different pattern and were not associated with the changes in plasma IGF-I or fertility.

Oocyte-mediated suppression of follicle-stimulating hormone- and insulin-like growth factor-induced secretion of steroids and inhibin-related proteins by bovine granulosa cells in vitro: Possible role of transforming growth factor alpha

The objective was to investigate the potential role of the oocyte in modulating proliferation and basal, FSH-induced and insulin-like growth factor (IGF)-induced secretion of inhibin A (inh A), activin A (act A), follistatin (FS), estradiol (E-2), and progesterone (P-4) by mural bovine granulosa cells. Cells from 4- to 6-mm follicles were cultured in serum-free medium containing insulin and androstenedione, and the effects of ovine FSH and IGF analogue (LR3-IGF-1) were tested alone and in the presence of denuded bovine oocytes (2, 8, or 20 per well). Medium was changed every 48 h, cultures were terminated after 144 h, and viable cell number was determined. Results are based on combined data from four independent cultures and are presented for the last time period only when responses were maximal. Both FSH and IGF increased (P < 0.001) secretion of inh A, act A, FS, E-2, and P-4 and raised cell number. In the absence of FSH or IGF, coculture with oocytes had no effect on any of the measured hormones, although cell number was increased up to 1.8-fold (P < 0.0001). Addition of oocytes to FSH-stimulated cells dose-dependently suppressed (P < 0.0001) inh A (6-fold maximum suppression), act A (5.5-fold), FS (3.6-fold), E-2 (4.6-fold), and P-4 (2.4-fold), with suppression increasing with FSH dose. Likewise, oocytes suppressed (P < 0.001) IGF-induced secretion of inh A, act A, FS, and E-2 (P < 0.05) but enhanced IGF-induced P-4 secretion (1.7-fold; P < 0.05). Given the similarity of these oocyte-mediated actions to those we observed previously following epidermal growth factor (EGF) treatment, we used immunocytochemistry to determine whether bovine oocytes express EGF or transforming growth factor (TGF) alpha. Intense staining with TGFalpha antibody (but not with EGF antibody) was detected in oocytes both before and after coculture. Experiments involving addition of TGFalpha to granulosa cells confirmed that the peptide mimicked the effects of oocytes on cell proliferation and on FSH- and IGF-induced hormone secretion. These experiments indicate that bovine oocytes secrete a factor(s) capable of modulating granulosa cell proliferation and responsiveness to FSH and IGF in terms of steroidogenesis and production of inhibin-related peptides, bovine oocytes express TGFalpha but not EGF, and TGFalpha is a prime candidate for mediating the actions of oocytes on bovine granulosa cells.

Avaliação de IGF-1 (Insulin-like growth factor-1), IGFBP-1 e IGFBP-3 (Insulin-like to growth binding protein-1 e 3) no fluído folicular de pacientes infertéis com endometriose

Resumo não disponível.

Expressão de mRNA e autofosforilação do receptor de IGF-I (insulin-like growth factor I) em miométrio e mioma humano

Resumo não disponível.

Association of an insulin-like growth factor 1 gene microsatellite with phenotypic variation and estimated breeding values of growth traits in Canchim cattle

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effect of insulin-like growth factor-1 during in vitro oocyte maturation and in vitro culture of bovine embryos

Avaliaram-se o efeito do IGF-I na maturação in vitro (MIV) (experimento I) e no desenvolvimento embrionário (DE) (experimento II) de oócitos bovinos fecundados in vitro, quanto às taxas de clivagem (TC), de blastocistos (TB) e de eclosão (TE). Para MIV, complexos cumulus-oócitos imaturos foram cultivados em meio TCM-199 suplementado com HEPES, bicarbonato e piruvato de sódio, aditivos, soro fetal bovino (meio B-199) e gonadotrofinas 14U/ml de PMSG e 7U/ml de hCG). Para o desenvolvimento embrionário, os oócitos/zigotos foram cultivados em meio B-199 com células epiteliais do oviduto bovino em suspensão sob óleo de silicone. As condições de cultivo in vitro para ambos os experimentos seguiram os tratamentos: 1- meio B-199 + 200 ng/ml IGF-I; 2- B-199 + 100 ng/ml IGF-I; 3- B-199 + 50 ng/ml IGF-I; 4- B-199 + 10 ng/ml IGF-I; 5- B-199 + 0 ng/ml IGF-I. Todas as culturas foram realizadas a 38,5° C em atmosfera com 5% de CO2 e os dados foram analisados pelo teste do qui-quadrado. No experimento I, não houve diferença (P>0,05) entre os tratamentos quanto às TC, TB e TE, quando o meio de MIV foi suplementado com IGF-I. No experimento II, a adição de IGF-I ao meio de DE resultou em aumento na TC (P<0,05) mas não influenciou a TB e a TE. A adição de 200 ng/ml de IGF-I ao meio DE melhorou a TC (71,1%) quando comparada com a TC dos grupos de 100 ng/ml de IGF-I (57,6%) ou controle (56,7%), entretanto não houve diferença quando comparada com a dos grupos de 50 ng/ml (69,4%) ou 10 ng/ml (73,1%) de IGF-I. Não houve efeito benéfico na adição de 10 a 200 ng/ml de IGF-I nos meios de MIV e de DE com relação ao desenvolvimento de embriões produzidos a partir de oócitos maturados e fecundados in vitro.

Proteínas ligantes do insulin-like growth factor (IGFBPs) e dominância folicular em vacas Bos taurus indicus puras e cruzadas

O objetivo deste estudo foi identificar um marcador bioquímico de folículos bovinos com diâmetro maior do que 10 mm, o qual poderia ser utilizado para identificar folículos dominantes nesta espécie. Líquido folicular era aspirado de folículos com diâmetros menores do que 5 mm, entre 5 e 10 mm e maiores do que 10 mm, provenientes de ovários de 37 fêmeas bovinas abatidas. Após aspiração, o líquido folicular (LF) era acondicionado em ependorfs etiquetados e congelados. Os padrões eletroforéticos em SDS-PAGE das proteínas do LF foram determinados e verificou-se que os folículos com diâmetro maior do que 10 mm apresentaram um polipeptídeo com PM entre 39 e 43 KDa identificado como a proteína ligante de IGF-3 (IGFBP-3), o qual não foi observado em folículos com diâmetro menor do que 5 mm e entre 5 e 10 mm. Este estudo sugere que este polipeptídeo possa ser utilizado como marcador bioquímico de folículos maiores do que 10 mm.

Hepatic mRNA expression and plasma levels of insulin-like growth factor-I (IGF-I) in broiler chickens selected for different growth rates

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expression and imprinting of insulin-like growth factor II (IGF2) and H19 genes in uterine leiomyomas

Genomic imprinting is defined as a gamete of origin-specific epigenetic modification of DNA leading to differential gene expression in the zygote. Several imprinted genes have been identified and some of them are associated with tumor development. We investigated the expression and the imprinting status of IGF2 and H19 genes in 47 uterine leiomyomas. Using allelic transcription assay, we detected the expression of the IGF2 gene in 10 of a total of 15 informative cases. No loss of imprinting, as determined by the finding of biallelic expression, was detected in any case. The expression of H19 gene was detected in 10 of 20 informative cases and the imprinting pattern was also maintained in all of them. Our data suggest that alterations in IGF2 and H19 genes expression by loss of imprinting do not occur in uterine leiomyomas. (C) 1999 Academic Press.

Relative expression of insulin like growth factor I (IGFI) and follicle stimulating hormone receptor (FSHR) in follicles and ovarian tissue from Bos primigenius indicus (Nelore)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)