PI3-Kinase/p38 Kinase-Dependent E2F1 Activation Is Critical for Pin1 Induction in Tamoxifen-Resistant Breast Cancer Cells
| Autor: | Hyun Jeong Nam, Jeong Woon Lee, Keon Wook Kang, Jeong-Hyun Shim, Youngsup Song, Kwang Youl Lee |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Vascular Endothelial Growth Factor A
Antineoplastic Agents Hormonal Blotting Western Breast Neoplasms Enzyme-Linked Immunosorbent Assay Biology p38 Mitogen-Activated Protein Kinases Phosphatidylinositol 3-Kinases Genes Reporter Cell Line Tumor Humans IL-2 receptor Gene Silencing RNA Small Interfering skin and connective tissue diseases Luciferases Molecular Biology Interleukin 3 CD40 Kinase Janus kinase 3 ZAP70 Cell Biology General Medicine Articles Peptidylprolyl Isomerase Up-Regulation Gene Expression Regulation Neoplastic NIMA-Interacting Peptidylprolyl Isomerase Tamoxifen Drug Resistance Neoplasm biology.protein Cancer research Interleukin 12 Female Signal transduction E2F1 Transcription Factor Signal Transduction |
| Popis: | Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem in breast cancer patients. We have shown that Pin1, a peptidyl prolyl isomerase, is consistently overexpressed in TAM-resistant MCF-7 cells (TAMR-MCF-7 cells) and plays a key role in the enhanced angiogenic potential of TAMR-MCF-7 cells. In the present study, we focused on signaling pathways for Pin1 up-regulation in TAMR-MCF-7 cells. Relative to MCF-7 cells, Pin1 gene transcription and E2 transcription factor1 (E2F1) expression were enhanced in TAMR-MCF-7 cells. E2F1 siRNA significantly reduced both the protein expression and the promoter transcriptional activity of Pin1. Activities of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK) and p38 kinase were all higher in TAMR-MCF-7 cells than in control MCF-7 cells and the enhanced Pin1 and E2F1 expression in TAMR-MCF-7 cells was reversed by inhibition of PI3K or p38 kinase. Moreover, the higher production of vascular endothelial growth factor (VEGF) in TAMR-MCF-7 cells was significantly diminished by suppression of PI3K or p38 kinase. These results suggest that Pin1 overexpression and subsequent VEGF production in TAMR-MCF-7 cells are mediated through PI3-kinase or p38 kinase-dependent E2F1 activation. |
| Databáze: | OpenAIRE |
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