Gene interactions and pathways from curated databases and text-mining
Leukemia 2004, PMID: 15129224

Hydroquinone modulates the GM-CSF signaling pathway in TF-1 cells.

Zheng, J H; Pyatt, D W; Gross, S A; Le, A T; Kerzic, P J; Irons, R D

Human leukemogens, including alkylating chemotherapeutic agents and benzene, enhance granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent proliferation of human CD34+ bone marrow (BM) cells. The extracellular signal-regulated kinase (ERK) pathway plays an important role in GM-CSF-dependent proliferation and also has been implicated in the pathogenesis of acute myelogenous leukemia. Therefore, we investigated the effects of the benzene metabolite, hydroquinone (HQ), on alterations in the GM-CSF signaling pathway in TF-1 erythroleukemia cells and human CD34+ BM cells. HQ treatment in TF-1 cells results in a strong proliferative response that is dependent on ERK activation and GM-CSF production. HQ also induces ERK-dependent AP-1 activation with concomitant increased transcriptional activity of AP-1 reporter gene. However, the kinetics of ERK activation are different between rhGM-CSF and HQ in TF-1 cells: rhGM-CSF results in immediate activation of ERK, whereas HQ activation of ERK is delayed. Further, HQ and rhGM-CSF together produce an immediate increase in ERK phosphorylation, which is sustained for over 48 h. HQ also stimulates colony formation, AP-1 DNA binding and GM-CSF production in human CD34+ BM cells. These results suggest that HQ stimulates proliferation via activation of ERK/AP-1 and is at least partially mediated via the production of GM-CSF.

Diseases/Pathways annotated by Medline MESH: Leukemia, Erythroblastic, Acute, Leukemia, Myeloid, Acute
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Text Mining Data

AP-1 → ERK: " HQ also induces ERK dependent AP-1 activation with concomitant increased transcriptional activity of AP-1 reporter gene "

ERK → rhGM-CSF: " Further, HQ and rhGM-CSF together produce an immediate increase in ERK phosphorylation, which is sustained for over 48 h. HQ also stimulates colony formation, AP-1 DNA binding and GM-CSF production in human CD34+ BM cells "

Manually curated Databases

No curated data.