ArticleJournal of cell communication and signaling2007
Specific inhibitor of MEK-mediated cross-talk between ERK and p38 MAPK during differentiation of human osteosarcoma cells.
Article in Journal of cell communication and signaling, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Erk inhibitors intercept Erk-mediated negative feedback while imposing cell-cycle arrest and activating p38.iScience · 2026Article
- Exploring the Effect of Resveratrol, Tyrosol, and Their Derivatives on Platelet-Activating Factor Biosynthesis in U937 Cells.Molecules (Basel, Switzerland) · 2024Article
- Anti‑oncogenic and pro‑myogenic action of the MKK6/p38/AKT axis induced by targeting MEK/ERK in embryonal rhabdomyosarcoma.Oncology reports · 2022Article
- Optical control of MAP kinase kinase 6 (MKK6) reveals that it has divergent roles in pro-apoptotic and anti-proliferative signaling.The Journal of biological chemistry · 2020Article
- Destined to Die: Apoptosis and Pediatric Cancers.Cancers · 2019Review
- Diosmetin inhibits osteoclast formation and differentiation and prevents LPS-induced osteolysis in mice.Journal of cellular physiology · 2019Article
- Construction of microRNA-messenger networks for human osteosarcoma.Journal of cellular physiology · 2019Article
- Dual Role For A MEK Inhibitor As A Modulator Of Inflammation And Host Defense Mechanisms With Potential Therapeutic Application In COPD.International journal of chronic obstructive pulmonary disease · 2019Article
- p38 Inhibition Ameliorates Inspiratory Resistive Breathing-Induced Pulmonary Inflammation.Inflammation · 2018Article
- Roles of Mitogen-Activated Protein Kinases in Osteoclast Biology.International journal of molecular sciences · 2018Review
- ERK1/2 and p38 regulate inter-individual variability in ozone-mediated IL-8 gene expression in primary human bronchial epithelial cells.Scientific reports · 2018Article
- Logic Modeling in Quantitative Systems Pharmacology.CPT: pharmacometrics & systems pharmacology · 2017Article
- CBX6 overexpression contributes to tumor progression and is predictive of a poor prognosis in hepatocellular carcinoma.Oncotarget · 2017Article
- Down-regulation of S100A9 inhibits osteosarcoma cell growth through inactivating MAPK and NF-κB signaling pathways.BMC cancer · 2016Article
- Combined inhibition of MEK and mTOR has a synergic effect on angiosarcoma tumorgrafts.International journal of oncology · 2015Article
- Quantitative analysis of castration resistant prostate cancer progression through phosphoproteome signaling.BMC cancer · 2014Article
- Icariin promotes self-renewal of neural stem cells: an involvement of extracellular regulated kinase signaling pathway.Chinese journal of integrative medicine · 2014Article
- Bone formation induced by BMP-2 in human osteosarcoma cells.International journal of oncology · 2013Article
- p38 MAPK regulates the expression of ether à go-go potassium channel in human osteosarcoma cells.Radiology and oncology · 2013Article
- Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling.BMC cell biology · 2012Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma is the most common primary malignant bone tumor, accounting for approximately 20% of all primary sarcomas in bone. Although treatment modalities have been improved over the past decades, it is still a tumor with a high mortality rate in children and young adults. Based on histological considerations, osteosarcoma arises from impaired differentiation of these immature cells into more mature types and that correction of this impairment may reduce malignancy and increase the efficiency of chemotherapy. The purpose of this study was to determine the effect of specific inhibitors of MAPK extracellular signaling-regulated kinase (ERK) kinase (MEK) and p38 on the differentiation of human osteosarcoma cell line SaOS-2 cells. We found that PD98059, a specific inhibitor of MEK, inhibited the serum-stimulated proliferation of SaOS-2 cells; whereas SB203580, a specific inhibitor of p38 MAPK, had little effect on it. SB203580 suppressed ALPase activity, gene expression of type I collagen, and expression of ALP and BMP-2 mRNAs; whereas PD98059 upregulated them dose dependently. In addition, immunoblot and immunostaining analysis revealed that phosphorylation of ERK was increased by treatment with SB203580; whereas PD98059 increased the phosphorylation of p38, which implies a seesaw-like balance between ERK and p38 phosphorylation. We suggest that osteosarcoma cell differentiation is regulated by the balance between the activities of the ERK and p38 pathways and that the MEK/ERK pathway negatively regulates osteosarcoma cell differentiation, whereas the p38 pathway does so positively. MEK inhibitor may thus be a good candidate for altering the expression of the osteosarcoma malignant phenotype.
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Registered trials
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