Insulin-like growth factor binding protein-2 is a novel mediator of p53 inhibition of insulin-like growth factor signaling

Grimberg, Adda; Coleman, Carrie M.; Shi, Zonggao; Burns, Timothy F.; MacLachlan, Timothy K.; Wang, Wenge; El‐Deiry, Wafik S.

doi:10.4161/cbt.5.10.3455

Cited by 39 publications

(34 citation statements)

References 49 publications

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“…Indeed, induction of PTEN downregulates IGFBP2 expression in glioblastoma and prostate cancer cells (Levitt et al, 2005;Mehrian-Shai et al, 2007). On the other hand, the p53 tumor suppressor is suggested to be a transcription factor that stimulates IGFBP2 expression (Grimberg et al, 2006). Hypoxia-induced expression of IGFBP2 mediated by hypoxia inducible factor 1 (HIF1 ), has also been demonstrated (Feldser et al, 1999).…”

Section: Proposed Physiological Functions Of Igfbp2mentioning

confidence: 97%

Insulin-Like Growth Factor Binding Protein-2: A Possible Regulator of Invasive Growth in Glioblastoma

Kataoka¹

2011

Molecular Targets of CNS Tumors

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Section: Proposed Physiological Functions Of Igfbp2mentioning

confidence: 97%

Insulin-Like Growth Factor Binding Protein-2: A Possible Regulator of Invasive Growth in Glioblastoma

Kataoka¹

2011

Molecular Targets of CNS Tumors

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“…Soluble IGFBP-2 binds to IGFs and consequently inhibits IGF signaling in various human cancers, including lung cancer. 19,[32][33][34] Membrane-associated IGFBP-2 stimulates or inhibits cell proliferation and migration through a direct binding to serum and extracellular matrix molecules, such as cell surface integrin receptors, proteoglycans, and heparin. [2][3][4][5]35 Meanwhile, a number of studies demonstrate that intracellular IGFBP-2 promotes cancer cell growth in various cell types.…”

Section: Discussionmentioning

confidence: 99%

Role of Insulin-Like Growth Factor Binding Protein 2 in Lung Adenocarcinoma

Migita

Narita

Asaka

et al. 2010

The American Journal of Pathology

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Insulin-like growth factor (IGF) signaling plays a pivotal role in cell proliferation and mitogenesis. Secreted IGFbinding proteins (IGFBPs) are important modulators of IGF bioavailability; however, their intracellular functions remain elusive. We sought to assess the antiapoptotic properties of intracellular IGFBP-2 in lung adenocarcinomas. IGFBP-2 overexpression resulted in a decrease in procaspase-3 expression; however, it did not influence the phosphorylation status of either IGF receptor or its downstream targets, including Akt and extracellular signal-regulated kinase. Apoptosis induced by camptothecin was significantly inhibited by IGFBP-2 overexpression in NCI-H522 cells. Conversely, selective knockdown of IGFBP-2 using small-interfering RNA resulted in an increase in procaspase-3 expression and sensitization to camptothecin-induced apoptosis in NCI-H522 cells. LY294002, an inhibitor of phosphatidylinositol 3-kinase, caused a decrease in IGFBP-2 levels and enhanced apoptosis in combination with camptothecin. Immunohistochemistry demonstrated that intracellular IGFBP-2 was highly expressed in lung adenocarcinomas compared with normal epithelium. Intracellular IGFBP-2 and procaspase-3 were expressed in a mutually exclusive manner. These findings suggest that intracellular IGFBP-2 regulates caspase-3 expression and contributes to the inhibitory effect on apoptosis independent of IGF. IGFBP-2, therefore, may offer a novel therapeutic target and serve as an antiapoptotic biomarker for lung adenocarcinoma.

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“…It can activate mitochondrial caspases, which cleave MAP kinases (activators of CDC2 kinases and cell cycle at G2/M phase; Marchetti et al 2004) and induce apoptosis-related events (Braithwaite et al 2006, Chowdhury et al 2006. When concerned with the role of p53 in controlling secretory activity, it is able to suppress growth factor secretion (VEGF, Hassan et al 2006) and insulin-like growth factor binding proteins (Grimberg et al 2006), and to promote vasopressin and catecholamine secretion (Chernigovskaya et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Transcription factor p53 can regulate proliferation, apoptosis and secretory activity of luteinizing porcine ovarian granulosa cell cultured with and without ghrelin and FSH

Sirotkin¹,

Benco²,

Tandlmajerová³

et al. 2008

Reproduction

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The aim of our in vitro experiments was to examine the role of transcription factor p53 in controlling the basic functions of ovarian cells and their response to hormonal treatments. Porcine ovarian granulosa cells, transfected and non-transfected with a gene construct encoding p53, were cultured with ghrelin and FSH (all at concentrations of 0, 1, 10, or 100 ng/ml). Accumulation of p53, of apoptosisrelated (MAP3K5) and proliferation-related (cyclin B1) substances was evaluated by immunocytochemistry. The secretion of progesterone (P 4 ), oxytocin (OT), prostaglandin F (PGF), and E (PGE) was measured by RIA. Transfection with the p53 gene construct promoted accumulation of this transcription factor within cells. It also stimulated the expression of a marker of apoptosis (MAP3K5). Over-expression of p53 resulted in reduced accumulation of a marker of proliferation (cyclin B1), P 4 , and PGF secretion and increased OT and PGE secretion. Ghrelin, when added alone, did not affect p53 or P 4 , but reduced MAP3K5 and increased PGF and PGE secretion. Over-expression of p53 reversed the effect of ghrelin on OT, caused it to be inhibitory to P 4 secretion, but did not modify its action on MAP3K5, PGF, or PGE. FSH promoted the accumulation of p53, MAP3K5, and cyclin B1; these effects were unaffected by p53 transfection. These multiple effects of the p53 gene construct on luteinizing granulosa cells, cultured with and without hormones 1) demonstrate the effects of ghrelin and FSH on porcine ovarian cell apoptosis and secretory activity, 2) confirm the involvement of p53 in promoting apoptosis and inhibiting P 4 secretion in these cells, 3) provide the first evidence that p53 suppress proliferation of ovarian cells, 4) provide the first evidence that p53 is involved in the control of ovarian peptide hormone (OT) and prostaglandin (PGF and PGE) secretion, and 5) suggest that p53 can modulate, but probably not mediate, the effects of ghrelin and FSH on the ovary. Reproduction (2008) 136 611-618

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Insulin-like growth factor binding protein-2 is a novel mediator of p53 inhibition of insulin-like growth factor signaling

Cited by 39 publications

References 49 publications

Insulin-Like Growth Factor Binding Protein-2: A Possible Regulator of Invasive Growth in Glioblastoma

Insulin-Like Growth Factor Binding Protein-2: A Possible Regulator of Invasive Growth in Glioblastoma

Role of Insulin-Like Growth Factor Binding Protein 2 in Lung Adenocarcinoma

Transcription factor p53 can regulate proliferation, apoptosis and secretory activity of luteinizing porcine ovarian granulosa cell cultured with and without ghrelin and FSH

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