The observation that p53 mutation is strongly correlated with VEGF expression and increased vascular density demonstrates the significance of understanding the mechanisms utilized by p53 to control angiogenesis. Towards deciphering the role of p53 in regulating angiogenesis, three genes identified by gene array technology as p53- regulated have been chosen for further examination. Cutaneous fatty acid binding protein (cFABP), connective tissue growth factor (CTGF) and endothelial and smooth muscle cell-derived neuropilin-like molecule (ESDN) are regulated in a p53-dependent manner following induction by pl4ARF. The interest in each lies with their ability to alter VEGF expression or activity. The expression of cFABP, CTGF or ESDN has not previously been linked to p53 expression, an observation that may provide insight into the regulation of VEGF activities by p53. Given these observations, the focus of this proposed study is to decipher the roles, either separately or collectively, of cFABP, CTGF and ESDN in the regulation of YEGF-mediated tumor angiogenesis and metastasis. The findings of this study will allow a more thorough understanding of p53-mediated signaling in tumor angiogenesis and invasion.
| LaRusch, Gretchen A; Jackson, Mark W; Dunbar, James D et al. (2007) Nutlin3 blocks vascular endothelial growth factor induction by preventing the interaction between hypoxia inducible factor 1alpha and Hdm2. Cancer Res 67:450-4 |
| Jackson, Mark W; Patt, Linnea E; LaRusch, Gretchen A et al. (2006) Hdm2 nuclear export, regulated by insulin-like growth factor-I/MAPK/p90Rsk signaling, mediates the transformation of human cells. J Biol Chem 281:16814-20 |
| Patton, John T; Mayo, Lindsey D; Singhi, Aatur D et al. (2006) Levels of HdmX expression dictate the sensitivity of normal and transformed cells to Nutlin-3. Cancer Res 66:3169-76 |
