Mutant V600E BRAF Increases Hypoxia Inducible Factor-1α Expression in Melanoma

@article{Kumar2007MutantVB,
  title={Mutant V600E BRAF Increases Hypoxia Inducible Factor-1$\alpha$ Expression in Melanoma},
  author={Suresh M. Kumar and Hong Yu and R. Edwards and Lianjun Chen and S. Kazianis and P. Brafford and G. Acs and M. Herlyn and Xiaowei Xu},
  journal={Cancer Research},
  year={2007},
  volume={67},
  pages={3177-3184}
}
Mutations in the BRAF serine/threonine kinase gene are frequently found in cutaneous melanomas. Activation of hypoxia inducible factor-1alpha (HIF-1alpha) in response to both hypoxic stress and oncogenic signals has important implications in cancer development and progression. Here, we report that mutant BRAF(V600E) increases HIF-1alpha expression in melanoma cells. Our microarray profiling data in 35 melanoma and melanocyte cell lines showed that HIF-1alpha gene expression was significantly… Expand
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References

SHOWING 1-10 OF 40 REFERENCES
Suppression of BRAF(V599E) in human melanoma abrogates transformation.
Activating mutations in the BRAF serine/threonine kinase are found in >70% of human melanomas, of which >90% are BRAF(V599E). We sought to investigate the role of the BRAF(V599E) allele in malignantExpand
Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors.
TLDR
The mechanistic underpinnings by which mutant (V599E)B-RAF promotes melanoma development are identified and the effectiveness of targeting this protein to inhibit melanoma tumor growth is shown. Expand
BRAF somatic mutations in malignant melanoma and melanocytic naevi
TLDR
Preclinical and early clinical studies predict that RAF/MEK/ERK pathway inhibitors will have therapeutic activity towards melanoma, but that tumour subclassification by BRAF/NRAS mutational status may be necessary to evaluate their efficacy. Expand
Mutations of the BRAF gene in human cancer
TLDR
BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers, with a single substitution (V599E) accounting for 80%. Expand
HIF-1α Induces Genetic Instability by Transcriptionally Downregulating MutSα Expression
TLDR
It is demonstrated that HIF-1α is responsible for genetic instability at the nucleotide level by inhibiting MSH2 and MSH6 , thereby decreasing levels of the MSH 2-MSH6 complex, MutSα, which recognizes base mismatches. Expand
Mutations of the BRAF gene in ulcerative colitis‐related colorectal carcinoma
TLDR
The data indicate that BRAF mutations are not an initiating event in UC‐related carcinogenesis and are associated with mismatch‐repair deficiency through hMLH1‐promoter hypermethylation. Expand
Endothelial apoptosis in Braf-deficient mice
TLDR
It is shown that mice with a targeted disruption in the Braf gene die of vascular defects during mid-gestation, and this work provides the first genetic evidence for an essential role of a Raf gene in the regulation of programmed cell death. Expand
HIF‐1α is required for solid tumor formation and embryonic vascularization
TLDR
The essential role of HIF‐1α in controlling both embryonic and tumorigenic responses to variations in microenvironmental oxygenation is demonstrated. Expand
Ras-dependent induction of HIF-1α785 via the Raf/MEK/ERK pathway: a novel mechanism of Ras-mediated tumor promotion
TLDR
It is found that the Ras oncogene regulates Hif-1α785 expression via the Raf/MEK/ERK pathway, and that both phorbol ester and epidermal growth factor also induced HIF-1 α785 via the same pathway. Expand
Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation.
TLDR
Constutively activated ERK is identified in almost all melanoma cell lines and in tumor tissues tested, which is in contrast to normal melanocytes and several early stage radial growth phase melanoma lines where ERK can be activated by serum or growth factors. Expand
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3
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