Reference - Detail
| RRC ID | 42703 |
|---|---|
| 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 |
| Abstract |
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. |
| Volume | 16(3) |
| Pages | 202-10 |
| Published | 2006-6-1 |
| DOI | 10.1016/j.ghir.2006.05.002 |
| PII | S1096-6374(06)00068-2 |
| PMID | 16844395 |
| 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* |
| IF | 1.618 |
| Times Cited | 11 |
| WOS Category | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
| Resource | |
| Human and Animal Cells | HHUA(RCB0658) |