ArticleMolecular biology of the cell2005
Involvement of PI3K and MAPK signaling in bcl-2-induced vascular endothelial growth factor expression in melanoma cells.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 89 citations in OpenAlex.
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- Integrative network toxicology, molecular dynamics and transcriptional analysis elucidate DEHP-induced cardiovascular dysfunction.Toxicology research · 2025Article
- BDNF and its signaling in cancer.Journal of cancer research and clinical oncology · 2023Review
- Metabolic reprogramming in Rheumatoid Arthritis Synovial Fibroblasts: A hybrid modeling approach.PLoS computational biology · 2022Article
- Thymoquinone Plus Immunotherapy in Extra-Pulmonary Neuroendocrine Carcinoma: Case Series for a Novel Combination.Current oncology (Toronto, Ont.) · 2022Article
- Targeting the anti-apoptotic Bcl-2 family proteins: machine learning virtual screening and biological evaluation of new small molecules.Theranostics · 2022Article
- Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer.Cells · 2020Review
- Resistance of melanoma cells to anticancer treatment: a role of vascular endothelial growth factor.Postepy dermatologii i alergologii · 2020Review
- Cholinergic α5 nicotinic receptor is involved in the proliferation and invasion of human prostate cancer cells.Oncology reports · 2020Article
- Angiogenesis in Gynecological Cancers: Role of Neurotrophins.Frontiers in oncology · 2019Review
- Semaphorin 5A drives melanoma progression: role of Bcl-2, miR-204 and c-Myb.Journal of experimental & clinical cancer research : CR · 2018Article
- Resistance to apoptosis in Leishmania infantum-infected human macrophages: a critical role for anti-apoptotic Bcl-2 protein and cellular IAP1/2.Clinical and experimental medicine · 2018Article
- Knockdown of CLDN6 inhibits cell proliferation and migration via PI3K/AKT/mTOR signaling pathway in endometrial carcinoma cell line HEC-1-B.OncoTargets and therapy · 2018Article
- Luteolin induces apoptosisOncology letters · 2017Article
- Insufficient Radiofrequency Ablation Treated Hepatocellular Carcinoma Cells Promote Metastasis by Up-Regulation ITGB3.Journal of Cancer · 2017Article
- Cancer Immune Equilibrium and Schizophrenia Have Similar Interferon-γ, Tumor Necrosis Factor-α, and Interleukin Expression: A Tumor Model of Schizophrenia.Schizophrenia bulletin · 2016Article
- Article
- Broad targeting of resistance to apoptosis in cancer.Seminars in cancer biology · 2015Review
- Verrucarin A alters cell-cycle regulatory proteins and induces apoptosis through reactive oxygen species-dependent p38MAPK activation in the human breast cancer cell line MCF-7.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have previously demonstrated that bcl-2 overexpression in tumor cells exposed to hypoxia increases the expression of vascular endothelial growth factor (VEGF) gene through the hypoxia-inducible factor-1 (HIF-1). In this article, we demonstrate that exposure of bcl-2 overexpressing melanoma cells to hypoxia induced phosphorylation of AKT and extracellular signal-regulated kinase (ERK)1/2 proteins. On the contrary, no modulation of these pathways by bcl-2 was observed under normoxic conditions. When HIF-1alpha expression was reduced by RNA interference, AKT and ERK1/2 phosphorylation were still induced by bcl-2. Pharmacological inhibition of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways reduced the induction of VEGF and HIF-1 in response to bcl-2 overexpression in hypoxia. No differences were observed between control and bcl-2-overexpressing cells in normoxia, in terms of VEGF protein secretion and in response to PI3K and MAPK inhibitors. We also demonstrated that RNA interference-mediated down-regulation of bcl-2 expression resulted in a decrease in the ERK1/2 phosphorylation and VEGF secretion only in bcl-2-overexpressing cell exposed to hypoxia but not in control cells. In conclusion, our results indicate, for the first time, that bcl-2 synergizes with hypoxia to promote expression of angiogenesis factors in melanoma cells through both PI3K- and MAPK-dependent pathways.
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