Hypoxia-inducible factor-1 in tumour angiogenesis

Figure 2 Signal transduction pathway in HIF-1α regulation. Oncogenes, growth factors and hypoxia have been documented to regulate HIF-1α protein and increase its transactivity. PI-3K/Akt, Raf-1/MEK/ERK1/2 and p38/JNK pathways were activated in response to oncogenes, growth factors and stress activators such as hypoxia, and carcinogens to different ex-tent in a cell type- and stimulus type-specific manner. GSK and mTOR were two target events of Akt and could contribute to decreasing HIF-1α degradation and increasing HIF-1α pro-tein synthesis. Activated ERK1/2 could mainly up-regulate