Characterization of an Antibody That Can Detect an Activated IGF-I Receptor in Human Cancers

Rubini, Michele; D'Ambrosio, Consuelo; Carturan, S.; Yumet, Gladys; Catalano, Edison; Shan, Simei; Huang, Ziwei; Criscuolo, Mario; Pifferi, M.; Baserga, Renato

doi:10.1006/excr.1999.4562

Cited by 17 publications

(20 citation statements)

References 40 publications

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“…We have found that medulloblastoma biopsies demonstrated cells with the phosphorylated (active) form of the IGF-IR, as shown by anti-pY1316 antibody staining (Rubini et al, 1999). Additionally, we examined four mouse BsB8,BsB13) and three human (Daoy, TE-671, D283 Med) medulloblastoma cell lines that are all positive for neuronal markers such as synaptophysin, class III b-tubulin and neuro®lament proteins, and are negative for glial ®brilliary acidic protein (GFAP).…”

Section: Introductionmentioning

confidence: 94%

“…Recently an antibody against the phosphorylated (active) form of the IGF-IR has been developed and characterized by Rubini et al (1999). This antibody speci®cally recognizes phosphotyrosine 1316 (pY1316) of the b subunit of IGF-IR, and does not cross-react with the corresponding moiety of the activated insulin receptor (Rubini et al, 1999).…”

Section: Activity Of the Igf-ir System In Biopsies From Patients Withmentioning

confidence: 99%

“…This antibody speci®cally recognizes phosphotyrosine 1316 (pY1316) of the b subunit of IGF-IR, and does not cross-react with the corresponding moiety of the activated insulin receptor (Rubini et al, 1999). To determine whether IGF-IR is activated in human medulloblastomas in vivo, para n sections of medulloblastoma biopsies were stained with the anti-pY1316 antibody.…”

Section: Activity Of the Igf-ir System In Biopsies From Patients Withmentioning

confidence: 99%

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Activation of the IGF-IR system contributes to malignant growth of human and mouse medulloblastomas

et al. 2001

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Section: Introductionmentioning

confidence: 94%

Section: Activity Of the Igf-ir System In Biopsies From Patients Withmentioning

confidence: 99%

Section: Activity Of the Igf-ir System In Biopsies From Patients Withmentioning

confidence: 99%

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Activation of the IGF-IR system contributes to malignant growth of human and mouse medulloblastomas

et al. 2001

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“…After air-drying, the cover-slips were incubated overnight with the rabbit polyclonal anti-pY1316 IGF-1R antibody (Rubini et al 1999) at a concentration of 1/150 in PBS for 24 h at r/t. The antibody recognises the phosphorylated tyrosine 1316 residue located in the C terminus of the IGF-1R and does not cross-react with the insulin receptor.…”

Section: Phosphorylated Igf-1rmentioning

confidence: 99%

Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells

Jones

Goddard²,

Gee³

et al. 2004

Endocr Relat Cancer

278

189

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De novo and acquired resistance to the anti-tumour drug gefitinib (ZD1839; Iressa), a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been reported. We have determined whether signalling through the IGF-I receptor (IGF-1R) pathway plays a role in the gefitinib-acquired resistance phenotype. Continuous exposure of EGFR-positive MCF-7-derived tamoxifen resistant breast cancer cells (TAM-R) to 1 mM gefitinib resulted in a sustained growth inhibition (90%) for 4 months before the surviving cells resumed proliferation. A stable gefitinibresistant subline (TAM/TKI-R) was established after a further 2 months and this showed no detectable basal phosphorylated EGFR activity. Compared with the parental TAM-R cells, the TAM/ TKI-R cells demonstrated (a) elevated levels of activated IGF-1R, AKT and protein kinase C (PKC)d, (b) an increased sensitivity to growth inhibition by the IGF-1R TKI AG1024 and (c) an increased migratory capacity that was reduced by AG1024 treatment. Similarly, the EGFR-positive androgen-independent human prostate cancer cell line DU145 was also continuously challenged with 1 mM gefitinib and, although substantial growth inhibition (60%) was seen initially, a gefitinibresistant variant (DU145/TKI-R) developed after 3 months. Like their breast cancer counterparts, the DU145/TKI-R cells showed increases in the levels of components of the IGF-1R signalling pathway and an elevated sensitivity to growth inhibition by AG1024 compared with the parent DU145 cell line. Additionally, DU145/TKI-R cell migration was also decreased by this inhibitor. We have therefore concluded that in breast and prostate cancer cells acquired resistance to gefitinib is associated with increased signalling via the IGF-1R pathway, which also plays a role in the invasive capacity of the gefitinib-resistant phenotype.

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“…To examine this, we carried out immunoperoxidase staining of tumor-bearing brain sections with antibodies against IGF1R, IRS-1, and phosphorylated (activated) forms of IGF1R and Akt. Using an antibody that specifically recognizes phosphotyrosine 1316 (pY1316) on the b subunit of IGF1R and does not crossreact with the corresponding moiety of the activated insulin receptor (Rubini et al, 1999), we found intense immunoreactive staining in the cytoplasm of tumor cells in MBs induced by Shh and Shh þ IGF2 (Figure 2a). In the adjacent cerebellar cortex, there was weak staining in the axonrich molecular layer, but no staining in cell bodies in the Purkinje or internal granule layers (Figure 2b).…”

mentioning

confidence: 99%

Sonic hedgehog and insulin-like growth factor signaling synergize to induce medulloblastoma formation from nestin-expressing neural progenitors in mice

et al. 2004

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Medulloblastoma (MB) is a malignant brain tumor that arises in the cerebellum of children. Activation of the Sonic hedgehog/Patched (Shh/Ptc) signaling pathway in neural progenitor cells of the cerebellum induces MBs in mice. The incomplete penetrance of tumor formation in mice, coupled with the low frequency of mutations in Shh/ Ptc pathway genes in human tumors, suggests that other signaling molecules cooperate with Shh to enhance MB formation. We modeled the ability of insulin-like growth factor (IGF) signaling to induce MB using the RCAS/tv-a system, which allows postnatal gene transfer and expression in a cell-type-specific manner. We used RCAS retroviral vectors to target expression of Shh, IGF2, and activated Akt to nestin-expressing neural progenitors in the cerebella of newborn mice. The incidence of Shhinduced tumor formation (15%) was enhanced by coexpression with IGF2 (39%) and Akt (48%). Neither IGF2 nor Akt caused tumors when expressed independently. The induced tumors showed upregulated expression of insulin receptor substrate 1 and phosphorylated forms of IGF1 receptor and Akt, mimicking activated IGF signaling found in human MBs. These results indicate that combined activation of the Shh/Ptc and IGF signaling pathways is an important mechanism in MB pathogenesis.

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Characterization of an Antibody That Can Detect an Activated IGF-I Receptor in Human Cancers

Cited by 17 publications

References 40 publications

Activation of the IGF-IR system contributes to malignant growth of human and mouse medulloblastomas

Activation of the IGF-IR system contributes to malignant growth of human and mouse medulloblastomas

Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells

Sonic hedgehog and insulin-like growth factor signaling synergize to induce medulloblastoma formation from nestin-expressing neural progenitors in mice

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