We have a suspicion that you are an automated web bot software, not a real user. To keep our site fast for other users, we have slowed down this page. The slowdown will gradually disappear. If you think this is a mistake, please contact us at genome-www@soe.ucsc.edu. Also note that all data for hgGeneGraph can be obtained through our public MySQL server and all our software source code is available and can be installed locally onto your own computer. If you are unsure how to use these resources, do not hesitate to contact us.
UCSC Genome Browser Gene Interaction Graph
Gene interactions and pathways from curated databases and text-mining
Int J Mol Med 2006, PMID: 16964427

UVB radiation induces expression of HIF-1alpha and VEGF through the EGFR/PI3K/DEC1 pathway.

Li, Yanhua; Bi, Zhigang; Yan, Bingfang; Wan, Yinsheng

EGFR is involved in the UV signal transduction pathway leading to skin cancer. UV radiation, mediated by EGFR, induces activation of PI3 kinase and AKT with a result of activation of a number of transcription factors. Transcription factor HIF-1alpha correlates with tumorigenicity and angiogenesis. Transcription factors DEC1 and DEC2 also play pivotal roles in multiple signaling pathways impacting various biological processes including development, cell differentiation, cell death, and oncogenesis. We investigated whether UV radiation and associated hypoxia induce expression of HIF-1alpha and its target genes such as VEGF and the signaling pathway mediating such responses. We found that UV radiation induced HIF-1alpha and VEGF protein expression in a dose- and time-dependent manner in cultured human keratinocytes. UV radiation also induced VEGF mRNA expression in a dose-dependent manner with maximum effect at 4 h post treatment, but did not affect HIF-1alpha mRNA expression. We also observed that UV radiation induced activation of EGFR in a time- and dose-dependent manner which was inhibited by EGFR inhibitor PD153035. In egfr (-/-) MEF cells, UV radiation did not induce HIF-1alpha and VEGF expression, in contrast, in egfr (+/+) MEF cells, UV radiation strongly induced HIF-1alpha and VEGF expression. EGFR kinase inhibitor, PD153035, inhibited UV-induced HIF-1alpha and VEGF protein expression in a dose-dependent manner. Further, we found that PI3K inhibitors, LY294002 and Wortmannin, inhibited HIF-1alpha and VEGF expression induced by UV radiation. In DEC1 (-/-) HaCat cells, UV radiation did not induce HIF-1alpha and VEGF expression, in contrast, in DEC1 (+/+) HaCat cells, UV radiation strongly enhanced HIF-1alpha and VEGF protein expression. We conclude that UV radiation induces HIF-1alpha and VEGF expression via the EGFR/PI3K/DEC1 signaling pathway.

Document information provided by NCBI PubMed

Text Mining Data

VEGF → HIF-1alpha: " In egfr ( -/- ) MEF cells, UV radiation did not induce HIF-1alpha and VEGF expression, in contrast, in egfr ( +/+ ) MEF cells, UV radiation strongly induced HIF-1alpha and VEGF expression "

VEGF → EGFR: " EGFR kinase inhibitor, PD153035, inhibited UV-induced HIF-1alpha and VEGF protein expression in a dose dependent manner "

HIF-1alpha → EGFR: " EGFR kinase inhibitor, PD153035, inhibited UV-induced HIF-1alpha and VEGF protein expression in a dose dependent manner "

VEGF → PI3K: " Further, we found that PI3K inhibitors, LY294002 and Wortmannin, inhibited HIF-1alpha and VEGF expression induced by UV radiation "

HIF-1alpha → PI3K: " Further, we found that PI3K inhibitors, LY294002 and Wortmannin, inhibited HIF-1alpha and VEGF expression induced by UV radiation "

Manually curated Databases

No curated data.