Fibroblast Growth Factor-1 Induced Promatrilysin Expression Through the Activation of Extracellular-regulated Kinases and STAT3
The MMP, matrilysin. (20MMP-7), has been shown to be overexpressed in prostate cancer cells and to increase prostate cancer cell invasion. Prostate stromal fibroblasts secrete factor(s), including fibroblast growth factor-1. (20FGF-1) that induces promatrilysin expression in LNCaP cells. In the pres...
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| Format: | Article |
| Language: | English |
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Elsevier
2002-01-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558602800483 |
| _version_ | 1819036806718423040 |
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| author | Thirupandiyur S. Udayakumar Mimi Suzanne Stratton Raymond B. Nagle George Timothy Bowden |
| author_facet | Thirupandiyur S. Udayakumar Mimi Suzanne Stratton Raymond B. Nagle George Timothy Bowden |
| author_sort | Thirupandiyur S. Udayakumar |
| collection | DOAJ |
| description | The MMP, matrilysin. (20MMP-7), has been shown to be overexpressed in prostate cancer cells and to increase prostate cancer cell invasion. Prostate stromal fibroblasts secrete factor(s), including fibroblast growth factor-1. (20FGF-1) that induces promatrilysin expression in LNCaP cells. In the present study, we investigated the signal transduction pathway involved in the FGF-1-induced expression of promatrilysin. FGF-1 treatment significantly increased the activation of extracellular signal-regulated kinases 1 and 2. (20ERK1 and ERK2). This induction was time-dependent and was sustained until 24 hours after treatment. Treating the cells with MEK1/2 inhibitor. (20PD98059) eliminated ERK activation completely and blocked FGF-1-mediated induction of promatrilysin expression. Transient transfection studies with human matrilysin promoter resulted in a four-to-five-fold increase in reporter luciferase enzyme activity that was blocked by the MEK1/2 inhibitor. (20PD98059). Serine phosphorylation of signal transducer and activator of transcription 3. (20STAT3) was observed after FGF-1 treatment and pretreatment with 20 µM PD98059 abolished STAT3 phosphorylation. Transient transfection with dominant negative STAT3 inhibited FGF-1-induced transactivation of the matrilysin promoter indicating that STAT3 plays an important role in FGF-1-induced matrilysin expression. We propose that the FGF-1-induced signaling pathway that leads to promatrilysin expression is ERK-dependent and leads to phosphorylation of Ser-727 on STAT3, phosphorylated STAT3, then binds and transactivates the matrilysin promoter. Our results demonstrate that ERK-MAP kinase and transcription factor STAT3 are important components of FGF-1-mediated signaling, which induce promatrilysin expression in LNCaP cells. |
| first_indexed | 2024-12-21T08:11:23Z |
| format | Article |
| id | doaj.art-7ded957d0d094692ad84e5cde334676a |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-21T08:11:23Z |
| publishDate | 2002-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-7ded957d0d094692ad84e5cde334676a2022-12-21T19:10:40ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022002-01-0141606710.1038/sj.neo.7900207Fibroblast Growth Factor-1 Induced Promatrilysin Expression Through the Activation of Extracellular-regulated Kinases and STAT3Thirupandiyur S. Udayakumar0Mimi Suzanne Stratton1Raymond B. Nagle2George Timothy Bowden3Departments of Radiation Oncology, University of Arizona Health Sciences Center, Tucson, AZ 85724, USADepartments of Radiation Oncology, University of Arizona Health Sciences Center, Tucson, AZ 85724, USADepartments of Pathology, University of Arizona Health Sciences Center, Tucson, AZ 85724, USADepartments of Radiation Oncology, University of Arizona Health Sciences Center, Tucson, AZ 85724, USAThe MMP, matrilysin. (20MMP-7), has been shown to be overexpressed in prostate cancer cells and to increase prostate cancer cell invasion. Prostate stromal fibroblasts secrete factor(s), including fibroblast growth factor-1. (20FGF-1) that induces promatrilysin expression in LNCaP cells. In the present study, we investigated the signal transduction pathway involved in the FGF-1-induced expression of promatrilysin. FGF-1 treatment significantly increased the activation of extracellular signal-regulated kinases 1 and 2. (20ERK1 and ERK2). This induction was time-dependent and was sustained until 24 hours after treatment. Treating the cells with MEK1/2 inhibitor. (20PD98059) eliminated ERK activation completely and blocked FGF-1-mediated induction of promatrilysin expression. Transient transfection studies with human matrilysin promoter resulted in a four-to-five-fold increase in reporter luciferase enzyme activity that was blocked by the MEK1/2 inhibitor. (20PD98059). Serine phosphorylation of signal transducer and activator of transcription 3. (20STAT3) was observed after FGF-1 treatment and pretreatment with 20 µM PD98059 abolished STAT3 phosphorylation. Transient transfection with dominant negative STAT3 inhibited FGF-1-induced transactivation of the matrilysin promoter indicating that STAT3 plays an important role in FGF-1-induced matrilysin expression. We propose that the FGF-1-induced signaling pathway that leads to promatrilysin expression is ERK-dependent and leads to phosphorylation of Ser-727 on STAT3, phosphorylated STAT3, then binds and transactivates the matrilysin promoter. Our results demonstrate that ERK-MAP kinase and transcription factor STAT3 are important components of FGF-1-mediated signaling, which induce promatrilysin expression in LNCaP cells.http://www.sciencedirect.com/science/article/pii/S1476558602800483matrilysinprostateSTAT3FGF-1LNCaP |
| spellingShingle | Thirupandiyur S. Udayakumar Mimi Suzanne Stratton Raymond B. Nagle George Timothy Bowden Fibroblast Growth Factor-1 Induced Promatrilysin Expression Through the Activation of Extracellular-regulated Kinases and STAT3 Neoplasia: An International Journal for Oncology Research matrilysin prostate STAT3 FGF-1 LNCaP |
| title | Fibroblast Growth Factor-1 Induced Promatrilysin Expression Through the Activation of Extracellular-regulated Kinases and STAT3 |
| title_full | Fibroblast Growth Factor-1 Induced Promatrilysin Expression Through the Activation of Extracellular-regulated Kinases and STAT3 |
| title_fullStr | Fibroblast Growth Factor-1 Induced Promatrilysin Expression Through the Activation of Extracellular-regulated Kinases and STAT3 |
| title_full_unstemmed | Fibroblast Growth Factor-1 Induced Promatrilysin Expression Through the Activation of Extracellular-regulated Kinases and STAT3 |
| title_short | Fibroblast Growth Factor-1 Induced Promatrilysin Expression Through the Activation of Extracellular-regulated Kinases and STAT3 |
| title_sort | fibroblast growth factor 1 induced promatrilysin expression through the activation of extracellular regulated kinases and stat3 |
| topic | matrilysin prostate STAT3 FGF-1 LNCaP |
| url | http://www.sciencedirect.com/science/article/pii/S1476558602800483 |
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