| First Author | Chevalier S | Year | 2002 |
| Journal | Mol Cell Endocrinol | Volume | 189 |
| Issue | 1-2 | Pages | 169-79 |
| PubMed ID | 12039075 | Mgi Jnum | J:76072 |
| Mgi Id | MGI:2178502 | Doi | 10.1016/s0303-7207(01)00728-6 |
| Citation | Chevalier S, et al. (2002) Vascular endothelial growth factor and signaling in the prostate: more than angiogenesis. Mol Cell Endocrinol 189(1-2):169-79 |
| abstractText | In cloning tyrosine kinase genes in dog prostate cells, a fragment of the vascular endothelial growth factor (VEGF) receptor 1 or Flt-1 was sequenced. To test for a functional protein, Flt-1 antibodies were used to probe immunoprecipitated tyrosine phosphorylated proteins. Western blotting revealed a major 170-180 kDa band and a few bands below 116 kDa in dog prostate and human prostatic carcinoma PC-3 cells, with higher levels in PC-3. Similar results were obtained with human placental membranes used as a source of Flt-1. That the major Flt-1 tyrosine phosphorylated protein was likely VEGF-R1 and part of VEGF signaling pathways was shown by enhanced level of only this protein when PC-3 cells were exposed to VEGF. Accordingly specific cell surface receptor complexes, displaced by VEGF but not EGF and compatible with Flt-1 in size, were revealed by chemical cross-linking after 125I-VEGF binding. Similarly to the prostatic neuroproduct, gastrin-releasing peptide/bombesin, VEGF directly triggered the tyrosine phosphorylation of focal adhesion kinase and stimulated PC-3 cell motility. The titration of prostate tissue sections with VEGF-A antibodies revealed a confined staining in chromogranin A and/or serotonin positive neuroendocrine (NE) cells, including in primary tumors and lymph node metastases. Given that NE differentiation is associated with advanced disease, that NE cells are a significant source of VEGF in prostatic tumors, and that VEGF directly act on prostate cancer cells in vitro, VEGF-A may be more than angiogenic in prostate cancer and hence favor progression by affecting tumor cells. |
