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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Boye, A. Kan, H. Wu, C. Jiang, Y. Yang, X. He, S. Yang, Y. |
| Description | Country affiliation: China Author Affiliation: Boye A ( Department of Pharmacology and Institute of Natural Medicine, Anhui Medical University, Hefei, 230032, China.) |
| Abstract | The aim of this study was to investigate the mitogen-activated protein kinase (MAPK) pathway, which crosstalk with TGF-β/Smad signaling via linker phosphorylation of Smad2/3 to promote hepatocarcinogenesis. After DEN-induced hepatocellular carcinoma (HCC) in rats showed increased phosphorylation of JNK1/2, p38, and ERK1/2, we next antagonized $TGF-β_{1}-induced$ phosphorylation of JNK1/2, p38, ERK1/2, Smad2/3 signaling in HepG2 cells using SP600125, SB203580, and PD98059, respectively. Cell proliferation and invasion were assessed by MTT assay and transwell invasion chambers, respectively. Smad2/3, Smad4, and Smad7 expressions and PAI-1 messenger RNA (mRNA) transcription were measured by using immuno-precipitation/immuno-blotting and real-time RT-PCR, respectively. All the MAPK-specific inhibitors suppressed cell invasion, while all but PD98059 suppressed cell proliferation. Both SP600125 and SB203580 blocked pSmad2C/L and oncogenic pSmad3L. PD98059 blocked pSmad2L but had no effect on elevated pSmad2C and oncogenic pSmad3L. All but PD98059 blocked Smad2/3/4 complex formation and restored Smad7 expression, while all the three MAPK-Specific inhibitors repressed PAI-1 mRNA transcription. Both SP600125 and SB203580 inhibited HepG2 cells’ proliferation and invasion by blocking oncogenic pSmad3L and Smad2/3/4 complex formation. PD98059 repressed PAI-1 mRNA by an unknown mechanism. |
| File Format | HTM / HTML |
| ISSN | 10104283 |
| Issue Number | 5 |
| Volume Number | 36 |
| e-ISSN | 14230380 |
| Journal | Tumor Biology |
| Language | English |
| Publisher | Springer |
| Publisher Date | 2015-05-01 |
| Publisher Place | Netherlands |
| Access Restriction | Subscribed |
| Subject Keyword | Discipline Medicine__semicolon__oncology Carcinogenesis Genetics Carcinoma, Hepatocellular Liver Neoplasms Smad Proteins Biosynthesis Transforming Growth Factor Beta Animals Chemically Induced Pathology Cell Proliferation Drug Effects Diethylnitrosamine Toxicity Flavonoids Administration & Dosage Gene Expression Regulation, Neoplastic Hep G2 Cells Humans Mitogen-activated Protein Kinase Kinases Antagonists & Inhibitors Neoplasm Invasiveness Plasminogen Activator Inhibitor 1 Rats Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Cancer Research |
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