Intracellular colocalization and interaction of IGF-binding protein-2 with the cyclin-dependent kinase inhibitor p21CIP1/WAF1 during growth inhibition

Terrien, Xavier; Bonvin, Elise; Corroyer, Sophie; Tabary, Olivier; Clément, Annick; Caude, Alexandra Henrion

doi:10.1042/bj20050517

Cited by 26 publications

(26 citation statements)

References 41 publications

(47 reference statements)

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“…These observations help validate the experimental approach and this ovary list. IGFBP2 is involved in growth inhibition in fetal development, and is abundant in Leydig cells (Wang et al 1994, Schneyer et al 2004, Terrien et al 2005, Yao 2005. AMH receptor 2 (AMHR2) is known to bind AMH to promote Mü llerian duct regression in the developing male, and to negatively regulate postnatal Leydig cell differentiation (Jamin et al 2002, Mendis-Handagama et al 2006.…”

Section: Discussionmentioning

confidence: 99%

Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: comparative candidate genes

Clement

Anway²,

Uzumcu³

et al. 2007

Reproduction

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Gene expression profiles during sex determination and gonadal differentiation were investigated to identify new potential regulatory factors. Embryonic day 13 (E13), E14, and E16 rat testes and ovaries were used for microarray analysis, as well as E13 testis organ cultures that undergo testis morphogenesis and develop seminiferous cords in vitro. A list of 109 genes resulted from a selective analysis for genes present in male gonadal development and with a 1.5-fold change in expression between E13 and E16. Characterization of these 109 genes potentially important for testis development revealed that cytoskeletal-associated proteins, extracellular matrix factors, and signaling factors were highly represented. Throughout the developmental period (E13-E16), sexenriched transcripts were more prevalent in the male with 34 of the 109 genes having testis-enriched expression during sex determination. In ovaries, the total number of transcripts with a 1.5-fold change in expression between E13 and E16 was similar to the testis, but none of those genes were both ovary enriched and regulated during the developmental period. Genes conserved in sex determination were identified by comparing changing transcripts in the rat analysis herein, to transcripts altered in previously published mouse studies of gonadal sex determination. A comparison of changing mouse and rat transcripts identified 43 genes with species conservation in sex determination and testis development. Profiles of gene expression during E13-E16 rat testis and ovary development are presented and candidate genes for involvement in sex determination and testis differentiation are identified. Analysis of cellular pathways did not reveal any specific pathways involving multiple candidate genes. However, the genes and gene network identified influence numerous cellular processes with cellular differentiation, proliferation, focal contact, RNA localization, and development being predominant. Reproduction (2007) 134 455-472

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Section: Discussionmentioning

confidence: 99%

Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: comparative candidate genes

Clement

Anway²,

Uzumcu³

et al. 2007

Reproduction

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“…Here, ECM-associated IGFBP-2 can act as a competitor for the IGF-I receptor (Pereira et al 2004), or the association of IGFBP-2 with the ECM itself may function as a cell targeting mechanism for IGFs. However, the findings that IGFBP-2 was also localized in the cytoplasm and on the nuclear surface (Hoeflich et al 2004) and interacts with the intracellular cell cycle inhibitor p21CIP1/WAF1 (Terrien et al 2005) show that IGFBP-2 exerts some of its actions directly within the cell. IGFBP-2 appears to have varying effects on different cell lines.…”

Section: Igfbp-2 Induction Of Genes Related To Apoptosismentioning

confidence: 99%

“…As a second pathway, IGFBP-2 has also been shown to bind to glycosaminoglycans, heparin, and proteoglycans (Arai et al 1996, Russo et al 1997, Conover & Khosla 2003, amongst others, by means of its heparinbinding domain (Russo et al 2005). In addition, IGFBP-2 was found to be localized on the cell surface (Pereira et al 2004, Russo et al 2005, in the cytoplasm, on the nuclear surface (Hoeflich et al 2004) and even within the nucleus (Terrien et al 2005).…”

Section: Introductionmentioning

confidence: 99%

IGF-independent effects of IGFBP-2 on the human breast cancer cell line Hs578T

Frommer¹,

Reichenmiller²,

Schütt³

et al. 2006

Journal of Molecular Endocrinology

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There is evidence that insulin-like growth factor-binding protein (IGFBP-2), a modulator of the actions of IGFs, also has IGF-independent effects in human tumor cell lines. These involve specific binding of IGFBP-2 to a5b1-integrin, followed by alterations in the phosphorylation status of downstream signaling molecules. Previously, IGFBP-2 has also been shown to be associated with cell proliferation, adhesion and migration. Here, we investigated direct effects of IGFBP-2 on apoptosis and alterations in the expression of related proteins. The breast cancer cell line Hs578T, which shows no IGFBP-2 production of its own and is independent of the IGF-I receptor, was treated with human recombinant IGFBP-2 in order to study the changes in gene expression induced by IGFBP-2. The methods employed for this purpose were oligonucleotide microarrays, real-time RT-PCR, western blotting, and immunoassays. Out of the 440 genes covered by the Oligo GEArray Human Cancer Microarray OHS-802, the expression of 77 genes was directly influenced by IGFBP-2. By the use of real-time quantitative RT-PCR, the gene expression of Nuclear Factor (NF)kB, p53, transforming growth factor b (TGF b-1), LAMB1 (Laminin, Beta 1), Bcl-2, and IIp45 was found to be significantly upregulated (by 1$2-to 3$05-fold; all P!0$001). Accordingly, NFkB, p53, and TGF b-1 proteins, as measured by Western blotting and immunoassay, were upregulated O1$5-fold. By using an ELISA-based and a flow cytometry-based apoptosis assay, IGFBP-2 was found to have a pro-apoptotic effect on Hs578T cells. Our results suggest that IGFBP-2-induced gene expressions are of functional significance for proliferation, cell adhesion, cell migration and apoptosis, and showed that IGFBP-2 can promote apoptosis in tumor cells independent of IGF.

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“…IGF binding to its binding protein protects the IGF from proteolytic degradation resulting in increased bioavailability of circulating IGFs. In addition to their role in regulating the bioavailability of circulating IGF, it has become clear that IGFBPs can also exert effects on numerous cell functions, including proliferation, survival, gene transcription and the initiation of apoptosis [33][34][35][36](see review Baxter, R 2014) [37].…”

Section: Insulin-like Growth Factor (Igf) Axismentioning

confidence: 99%

“…We have shown that IGFBP-2 could promote prostate tumour progression by acting as a growth promoter and as a survival factor against docetaxel-induced cell death [134]. It has also been shown that IGFBP-2 plays an important role in promoting the metastatic ability of many cells including human dermal fibroblasts, breast cancer and glioma cells [33][34][35] through the interaction with -1 integrin receptors via the RGD sequence of IGFBP-2 [135]. This interaction leads to inactivation of phosphatase and tensin homolog (PTEN), a tumour suppressor gene and the phosphatase that normally restrains the PI3K/Akt pathway [136].…”

Section: The Role Of Igf System In Mediating Emtmentioning

confidence: 99%

The Role of the IGF Axis in Epithelial-to-Mesenchymal Transition during the Progression of Prostate Cancer

Mansor¹,

Bahl²,

Holly³

et al. 2015

J. Anal. Oncol.

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Prostate cancer is the second most common lethal cancer in men worldwide. Despite the fact that the prognosis for patients with localized disease is good, many patients succumb to metastatic disease with the development of resistance to hormone treatments. This is normally termed castration-resistant prostate cancer (CRPC). The development of metastatic, castration-resistant prostate cancer has been associated with epithelial-to-mesenchymal transition (EMT), a process where cancer cells acquire a more mesenchymal phenotype with enhanced migratory potential, invasiveness and elevated resistance to apoptosis. The main event in EMT is the repression of epithelial markers such as E-cadherin and upregulation of mesenchymal markers such as N-cadherin, vimentin and fibronectin. The insulin-like growth factor (IGF) signalling axis is essential for normal development and maintenance of tissues, including that of the prostate, and dysregulation of this pathway contributes to prostate cancer progression and malignant transformation. It is becoming increasingly clear that one of the ways in which the IGF axis impacts upon cancer progression is through promoting EMT. This review will explore the role of EMT in prostate cancer progression with a specific focus on the involvement of the IGF axis and its downstream signalling pathways in regulating EMT in prostate cancer.Keywords: Epithelial-to-mesenchymal transition, insulin-like growth factor family, prostate cancer progression, lifestyle factors. PROSTATE CANCERProstate cancer is the second most common lethal cancer diagnosed in men. According to The American Cancer Society, it is estimated that more than 220 000 new cases of prostate cancer will occur in the United States during 2015 accounting for about 26% of all cancers in men with a mortality rate of 9%: the second highest cause of cancer deaths in men after lung cancer [1].Age is the biggest risk factor for PCa with the incidence of prostate cancer being higher in older men particularly in men aged 65 and above [2]. The incidence of, and mortality from, prostate cancer varies hugely within different racial and ethnic groups. Much higher incidence and death rates are reported in black men compared to other races [3,4]: the reasons underlying these observations are still unclear but both genetic and/or environmental influences may be involved. A number of epidemiology studies have also reported that family history is a risk factor for PCa-with approximately 5-10% of cases being attributable to inherited genetic factors or PCa susceptibility genes [5,6] The prognosis for patients with localized disease is good, however the morbidity and mortality for prostate cancer patients who develop metastatic disease is high [7]. Androgen deprivation therapy (ADT) which involves surgical or chemical castration plays an important role in the treatment and management of prostate cancer and is also utilised as an adjuvant or neo-adjuvant treatment for high-risk disease [8]. The response to the treatments is however temporary a...

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Intracellular colocalization and interaction of IGF-binding protein-2 with the cyclin-dependent kinase inhibitor p21CIP1/WAF1 during growth inhibition

Cited by 26 publications

References 41 publications

Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: comparative candidate genes

Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: comparative candidate genes

IGF-independent effects of IGFBP-2 on the human breast cancer cell line Hs578T

The Role of the IGF Axis in Epithelial-to-Mesenchymal Transition during the Progression of Prostate Cancer

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