Reference - Detail
|Author||Mochizuki T, Sakai K, Iwashita M.|
|Title||Effects of insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) on endometrial cancer (HHUA) cell apoptosis and EGF stimulated cell proliferation in vitro.|
|Journal||Growth Horm. IGF Res.|
OBJECTIVE:IGFBP-3 has been demonstrated to stimulate or inhibit cell proliferation independently of its ability to bind IGF and a specific IGFBP-3 receptor has been proposed. EGF has been implicated in the cancer development and carcinogenesis. Only limited data are available on the crosstalk between IGFBP-3 signaling and EGF induced cell survival and signal transduction. The current studies were undertaken to characterize IGFBP-3 binding to endometrial cancer cells (HHUA) and determine its biological effects, as well as whether IGFBP-3 exposure alters the cell proliferation stimulated by EGF.
METHODS:Cell proliferation and apoptosis were analyzed by ELISA using specific antibodies. The interaction between HHUA cell and IGFBP-3 was analyzed using a biosensor. The phosphorylation abundance of specific proteins and their phosphorylation in response to EGF and IGFBP-3 was analyzed by immunoprecipitation followed by immunoblotting.
RESULTS:Biosensor analysis showed that IGFBP-3 could bind to HHUA cell surface. IGFBP-3 inhibited BrdU uptake, potentiated ssDNA production and induced p53 in HHUA cells. Although EGF stimulated HHUA cell proliferation and Akt phosphorylation, IGFBP-3 inhibited cell proliferation and Akt phosphorylation that had been stimulated by EGF. However, EGF receptor phosphorylation and expression were not reduced by IGFBP-3. Since HHUA cells lack IGF receptors and do not show biological response to IGF these results suggest that IGFBP-3 can bind to HHUA cells, inhibit cell proliferation and induce apoptosis independently of its ability to bind to IGFs possibly by binding to an IGFBP-3 receptor.
CONCLUSIONS:Taken together these findings demonstrate that IGFBP-3 binds to HHUA cell surface, and inhibits cell division induced by EGF, possibly by modulating the EGF-mediated signal transduction system.
|MeSH||Antimetabolites, Antineoplastic / metabolism Apoptosis Biosensing Techniques Bromodeoxyuridine / metabolism Cell Membrane / chemistry Cell Membrane / metabolism Cell Proliferation / drug effects DNA, Single-Stranded / analysis DNA, Single-Stranded / metabolism Endometrial Neoplasms / chemistry Endometrial Neoplasms / metabolism* Epidermal Growth Factor / antagonists & inhibitors* Epidermal Growth Factor / pharmacology ErbB Receptors / metabolism* Female Humans Insulin-Like Growth Factor Binding Protein 3 / analysis Insulin-Like Growth Factor Binding Protein 3 / metabolism* Insulin-Like Growth Factor Binding Protein 3 / pharmacology Phosphorylation Proto-Oncogene Proteins c-akt / metabolism*|
|WOS Category||ENDOCRINOLOGY & METABOLISM CELL BIOLOGY|
|Human and Animal Cells|