Simian virus 40 large tumor antigen is unable to transform mouse embryonic fibroblasts lacking type 1 insulin-like growth factor receptor.

Sell, Christian; Rubini, Michele; Rubin, Raphael; Liu, Jeh-Ping; Efstratiadis, Argiris; Baserga, Renato

doi:10.1073/pnas.90.23.11217

Cited by 502 publications

(486 citation statements)

References 38 publications

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“…The ®nding that the complete absence of the IGF-IR inhibits transformation (Sell et al, 1993) is not invalidated by the present results, since a dominant negative mutant of the IGF-IR still causes apoptosis of LNCaP cells . The picture that emerges is that the IGF-IR (even at low levels) is crucial for transformation, but that it requires IRS-1 for this function.…”

Section: Effect Of Irs-1 On the Growth Of Lncap Cells In Nude Micementioning

confidence: 49%

IGF-I receptor signaling in a prostatic cancer cell line with a PTEN mutation

et al. 2000

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LNCaP prostatic cancer cells are characterized by having a PTEN mutation, low levels of type 1 insulinlike growth factor receptor (IGF-IR) and no IRS-1, one of the major substrates of the IGF-IR. The absence of IRS-1, an activator of PI3-kinase, is compensated in these cells by the mutation in PTEN, an inhibitor of PI3-kinase. However, IGF-IR signaling in the absence of IRS-1 can cause cell di erentiation and growth arrest. We hypothesized that these three characteristics may not be unrelated, speci®cally that, together, they may favor the metastatic spread of prostatic cancer cells without decreasing their growth potential. In support of this hypothesis, we report here that: (1) IRS-1 expression increases cell adhesion and decreases cell motility; (2) over-expression of the IGF-IR, in the absence of IRS-1, causes growth arrest and (3) a combination of IGF-IR and IRS-1 restores the transformed phenotype of LNCaP cells. These ®ndings suggest a mechanism by which prostatic cancer cells can achieve metastatic potential without interfering with their growth potential.

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Section: Effect Of Irs-1 On the Growth Of Lncap Cells In Nude Micementioning

confidence: 49%

IGF-I receptor signaling in a prostatic cancer cell line with a PTEN mutation

et al. 2000

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“…In transformed MEFs with high IGF-IR numbers, like R þ cells (Sell et al, 1993), IRS-1 is largely nuclear (Tu et al, 2002). In cells with lower numbers of IGF-IR (R12 cells, and other cell types), IRS-1 is confined to the cytoplasm.…”

Section: Resultsmentioning

confidence: 99%

“…By ChIPs, IRS-1 is detectable in the rDNA promoter (Chen et al, 2005). IGF-1 fails to translocate IRS-1 to nuclei of RÀ cells (Tu et al, 2002) that are MEFs with a targeted disruption of the IGF-IR genes (Sell et al, 1993). We asked whether nuclear IRS-1 in R þ cells would also increase transcription from RNA polymerase II promoters.…”

Section: Resultsmentioning

confidence: 99%

“…Figure 1a, shows that IGF-1 stimulation of R þ cells increases the activities of both c-myc and cyclin D1 promoters. As control, we used the parental cell line, RÀ cells (Sell et al, 1993) that do not express IGF-IRs. Stimulation of RÀ cells by IGF-1 did not increase activity of the promoters.…”

Section: Resultsmentioning

confidence: 99%

“…They have been described in previous papers (Sell et al, 1993;Reiss et al, 2001) and in the Results section.…”

Section: Methodsmentioning

confidence: 99%

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Nuclear insulin receptor substrate-1 activates promoters of cell cycle progression genes

Chen

Baserga

2007

Oncogene

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The insulin receptor substrate-1 (IRS-1) is a docking protein of the insulin-like growth factor-1 (IGF-1) receptor and of the insulin receptor. IRS-1 sends a strong mitogenic, anti-apoptotic signal and plays an important role in cell transformation and cancer. IRS-1 translocates to nuclei of cells, where it increases the activity of the rDNA, c-myc and cyclin D1 promoters. We show, by chromatin immunoprecipitation, occupancy by IRS-1 of the same promoters. Both promoter activation and promoter occupancy are IGF-1-dependent. In cells that respond to IGF-1 but in which IRS-1 does not translocate to nuclei, promoter occupancy is absent and promoter activation is absent or much reduced. Transcriptional activation of c-myc and cyclin D1 promoters by nuclear IRS-1 does not occur with a mutant, inactive IRS-1 protein (deletion of the phosphotyrosine-binding domain, PTB) and does not require PI3-kinase activity. Taken together, these results indicate a novel mechanism by which nuclear IRS-1 activates cell cycle genes.

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Differential roles of IRS-1 and SHC signaling pathways in breast cancer cells

et al. 1997

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Several polypeptide growth factors stimulate breast cancer growth and may be involved in tumor progression. However, the relative importance of diverse growth factor signaling pathways in the development and maintenance of the neoplastic phenotype is largely unknown. The activation of such growth factor receptors as the insulin‐like growth factor I receptor (IGF‐I R), erbB‐type receptors (erbB Rs) and FGF receptors (FGF Rs) controls the phenotype of a model breast cancer cell line MCF‐7. To evaluate the function of 2 post‐receptor signaling molecules, insulin receptor substrate‐1 (IRS‐1) (a major substrate of the IGF‐IR) and SHC (a common substrate of tyrosine kinase receptors), we developed several MCF‐7‐derived cell clones in which the synthesis of either IRS‐1 or SHC was blocked by antisense RNA. In MCF‐7 cells, down‐regulation of IRS‐1 by 80–85% strongly suppressed anchorage‐dependent and ‐independent growth and induced apoptotic cell death under growth factor‐ and estrogen‐reduced conditions. The reduction of SHC levels by approximately 50% resulted in the inhibition of monolayer and anchorage‐independent growth but did not decrease cell survival. Importantly, cell aggregation and the ability of cells to survive on the extracellular matrix were inhibited in MCF‐7/anti‐SHC clones, but not in MCF‐7/anti‐IRS‐1 clones. Cell motility toward IGF was not attenuated in any of the tested cell lines, but motility toward EGF was decreased in MCF‐7/anti‐SHC clones. Our results suggest that in MCF‐7 cells: 1) both IRS‐1 and SHC are implicated in the control of monolayer and anchorage‐independent growth; 2) IRS‐1 is critical to support cell survival; 3) SHC is involved in EGF‐dependent motility; and 4) normal levels of SHC, but not IRS‐1, are necessary for the formation and maintenance of cell‐cell interactions. Int. J. Cancer 72:828–834, 1997. © 1997 Wiley‐Liss, Inc.

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Simian virus 40 large tumor antigen is unable to transform mouse embryonic fibroblasts lacking type 1 insulin-like growth factor receptor.

Cited by 502 publications

References 38 publications

IGF-I receptor signaling in a prostatic cancer cell line with a PTEN mutation

IGF-I receptor signaling in a prostatic cancer cell line with a PTEN mutation

Nuclear insulin receptor substrate-1 activates promoters of cell cycle progression genes

Differential roles of IRS-1 and SHC signaling pathways in breast cancer cells

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