Inhibitory Effect of Small Interfering RNA Targeting Insulin-Like Growth Factor-I Receptor in Ovarian Cancer OVCAR3 Cells

2010 ◽  
Vol 25 (5) ◽  
pp. 545-552 ◽  
Author(s):  
Yuan An ◽  
Yan Cai ◽  
Yongmei Guan ◽  
Liying Cai ◽  
Yang Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Small Interfering Rna ◽  
Inhibitory Effect ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Rna Targeting ◽  
Growth Factor I ◽  
Interfering Rna

scholarly journals Aldosterone Stimulates Elastogenesis in Cardiac Fibroblasts via Mineralocorticoid Receptor-independent Action Involving the Consecutive Activation of Gα13, c-Src, the Insulin-like Growth Factor-I Receptor, and Phosphatidylinositol 3-Kinase/Akt

2009 ◽  
Vol 284 (24) ◽  
pp. 16633-16647 ◽  
Author(s):  
Severa Bunda ◽  
Yanting Wang ◽  
Thomas F. Mitts ◽  
Peter Liu ◽  
Sara Arab ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Mineralocorticoid Receptor ◽  
Small Interfering Rna ◽  
Cardiac Fibroblasts ◽  
Insulin Like Growth Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
Factor I ◽  
Growth Factor I ◽  
Interfering Rna

We previously demonstrated that aldosterone, which stimulates collagen production through the mineralocorticoid receptor (MR)-dependent pathway, also induces elastogenesis via a parallel MR-independent mechanism involving insulin-like growth factor-I receptor (IGF-IR) signaling. The present study provides a more detailed explanation of this signaling pathway. Our data demonstrate that small interfering RNA-driven elimination of MR in cardiac fibroblasts does not inhibit aldosterone-induced IGF-IR phosphorylation and subsequent increase in elastin production. These results exclude the involvement of the MR in aldosterone-induced increases in elastin production. Results of further experiments aimed at identifying the upstream signaling component(s) that might be activated by aldosterone also eliminate the putative involvement of pertussis toxin-sensitive Gαi proteins, which have previously been shown to be responsible for some MR-independent effects of aldosterone. Instead, we found that small interfering RNA-dependent elimination of another heterotrimeric G protein, Gα13, eliminates aldosterone-induced elastogenesis. We further demonstrate that aldosterone first engages Gα13 and then promotes its transient interaction with c-Src, which constitutes a prerequisite step for aldosterone-dependent activation of the IGF-IR and propagation of consecutive downstream elastogenic signaling involving phosphatidylinositol 3-kinase/Akt. In summary, the data we present reveal new details of an MR-independent cellular signaling pathway through which aldosterone stimulates elastogenesis in human cardiac fibroblasts.

scholarly journals Effects of Recombinant Human Insulin-Like Growth Factor I Administration on Growth Hormone (GH) Secretion, Both Spontaneous and Stimulated by GH-Releasing Hormone or Hexarelin, a Peptidyl GH Secretagogue, in Humans1

1999 ◽  
Vol 84 (1) ◽  
pp. 285-290
Author(s):  
E. Ghigo ◽  
L. Gianotti ◽  
E. Arvat ◽  
J. Ramunni ◽  
M. R. Valetto ◽  
...  
Keyword(s):  
Growth Factor ◽  
Negative Feedback ◽  
Inhibitory Effect ◽  
Insulin Like Growth Factor ◽  
Recombinant Human Insulin ◽  
Gh Secretion ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Hypothalamic Level

The negative feedback exerted by insulin-like growth factor I (IGF-I) on GH secretion occurs at the pituitary, as well as the hypothalamic level, via stimulation of SS and/or inhibition of GHRH release. In fact, recombinant human IGF-I (rhIGF-I) administration inhibits basal GH secretion, at least in fasted humans, though its effect on the GH response to GHRH is still controversial. GH secretagogues (GHS) are peptidyl and nonpeptidyl molecules that act on specific receptors at the pituitary and/or the hypothalamic level. Contrary to GHRH, the GH-releasing activity of GHS is strong, reproducible, and even partially refractory to inhibitory influences such as exogenous somatostatin. We studied the effects of rhIGF-I administration (20μ g/kg sc at 0 min) on GH secretion, either spontaneous or stimulated by GHRH (2 μg/kg iv at +180 min) or Hexarelin (HEX, 2.0 μg/kg iv at+ 180 min), a GHS, in eight normal young women (age, mean ± sem, 28.3 ± 1.2 yr; body mass index, 20.1± 0.5 kg/m2). rhIGF-I administration increased IGF-I levels (peak vs. baseline: 420.3 ± 30.5 vs. 274.4 ± 25.3 μg/L, P < 0.05) within the physiological range from +120 to +300 min. No variation in glucose or insulin levels was recorded. rhIGF-I did not reduce spontaneous GH secretion [areas under curves (AUC)0–300 min 140.6± 66.3 vs. 114.6 ± 32.1 μg/L·h], whereas it inhibited the GH response to both GHRH (AUC180–300 min 447.7 ± 159.4 vs. 715.9 ± 104.3 μg/L·h, P < 0.05) and HEX (620.3 ± 110.4 vs. 1705.9 ± 328.9 μg/L·h, P < 0.03). The percent inhibitory effect of rhIGF-I on the GH response to GHRH (41.7 ± 12.8%) was lower than that on the response to HEX (57.7 ± 11.0%). In fact, the GH response to GHRH alone was clearly lower than that to HEX alone (P < 0.05), whereas the GH responses to GHRH and HEX were similar after rhIGF-I. Our findings show that the sc administration of low rhIGF-I doses inhibits the GH response to GHRH and, even more, that to HEX; whereas, at least in this experimental design in fed conditions, it does not modify the spontaneous GH secretion. Because GHS generally show partial refractoriness to inhibitory inputs, including exogenous somatostatin, the present results point toward a peculiar sensitivity of GHS to the negative feedback action of IGF-I.

Insulin-like growth factor-I attenuates the inhibitory effect of type I collagen through β1 integrin receptor

2005 ◽  
Vol 336 (3) ◽  
pp. 836-841 ◽  
Author(s):  
Niraporn Chutivongse ◽  
Piyamas Sumrejkanchanakij ◽  
Tussanee Yongchaitrakul ◽  
Prasit Pavasant
Keyword(s):  
Growth Factor ◽  
Type I Collagen ◽  
Inhibitory Effect ◽  
Type I ◽  
Β1 Integrin ◽  
Insulin Like Growth Factor ◽  
Integrin Receptor ◽  
Factor I ◽  
Growth Factor I

scholarly journals Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort

2014 ◽  
Vol 112 (1) ◽  
pp. 162-166 ◽  
Author(s):  
J Ose ◽  
R T Fortner ◽  
H Schock ◽  
P H Peeters ◽  
N C Onland-Moret ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Growth Factor I ◽  
Tumour Characteristics
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