Vascular Endothelial Factor ( Vegf )

Decent Essays

Vascular endothelial factor (VEGF) is a potent angiogenic factor which plays an important role in regulating normal physiological and pathological angiogenesis. Correctly timed expression of VEGF at appropriate levels is crucial for normal development of vasculature and homeostasis, but also vital for solid tumour growth. VEGF is highly expressed in solid tumours and is required for the development and maintenance of blood vessels within the tumour, which is a prerequisite for successful tumour growth and metastasis.
A co-expression study was undertaken to evaluate the correlated expression of MDM2 and VEGF, finding that, over eight different cancer cell lines, higher MDM2 expression meant higher VEGF mRNA, with the cell lines with lost …show more content…

HIF-1 is comprised of two subunits: HIF-1β is constitutively expressed in the cell, however, HIF-1α is degraded under normoxic conditions. Following a decrease in cellular oxygen levels, HIF-1α is stabilised and, thus, the heterodimer can form. Overexpression of HIF-1α has been linked to angiogenesis, tumour invasion and a poor prognosis in many types of cancer [52–55]. The HIF-1 transcription factor binds to the 5’ flanking sequence of vegf and is essential for the transactivation of vegf during hypoxia.
It has been known for some time that hypoxia is a physiological inducer of tumour suppressor p53, with p53 protein levels increasing under hypoxic conditions. Since MDM2 is the most important negative regulator of p53, many groups began to look into the precise mechanism of the interaction between hypoxia and p53, and whether MDM2 was involved.
In 2005, a study showed that MDM2 positively activates HIF-1α in hypoxic tumour cells. Co-immunoprecipitation showed that MDM2 precipitates with HIF-1α, completely independently of p53 [56]. Evidence towards the involvement of MDM2 in the regulation HIF-1α expression under hypoxic conditions came from Lau et al.[57], who found that inhibitory effects on HIF-1α by the anti-cancer drug 3-(5’-hydroxymethyl-2’-furyl)-1-benzyl indazole (YC-1), was MDM2-dependent and that overexpression of MDM2 reversed its inhibitory effects.
Another study showed that nutlin-3

Get Access