Analysis of the cellular uptake and nuclear delivery of insulin-like growth factor binding protein-3 in human osteosarcoma cells
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1 juin 2010
- handle: 10670/1.yh8o27
- doi: 10.1002/ijc.26149
info:eu-repo/semantics/openAccess
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Carcinoma Cancers Malignancy (Cancer) Malignant tumorsCiter ce document
A. Laich et al., « Analysis of the cellular uptake and nuclear delivery of insulin-like growth factor binding protein-3 in human osteosarcoma cells », Elektronisches Publikationsportal der Österreichischen Akademie der Wissenschafte, ID : 10.1002/ijc.26149
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Résumé
Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) is an important regulator of cell proliferation and survival, which plays an important role in a variety of epithelial cancers, including prostate cancer, cervical cancer and breast cancer. IGFBP-3 was described as a tumor suppressor in the prostate and identified as a functional cellular target for the E7 oncoprotein of human papillomaviruses. IGFBP-3 interacts with IGF-I outside the cell; however, IGF-independent actions of IGFBP-3 were also described which are mediated by intracellular IGFBP-3, including nuclear IGFBP-3. The mechanisms by which extracellular proteins can reach the nucleus are still largely unknown. We show here that the addition of IGFBP-3 to living cells results in the rapid appearance of nuclear IGFBP-3 by confocal microscopy of IGFBP-3 uptake in live cells, supported by electron microscopy and cell fractionation studies. IGFBP-3 is internalized through a dynamin-dependent pathway, traffics through endocytic compartments and is finally delivered into the nucleus. We observed docking of IGFBP-3 containing structures to the nuclear envelope and found IGFBP-3 containing dot-like structures to permeate the nuclear envelope. In summary, our findings establish the pathway by which this tumor suppressor protein is delivered from extracellular space to the nucleus.