| Neurotrophins, NGF, NT-3, BDNF and NT4-5, are growth factor proteins key to the regulation of neuronal survival, death of differentiation. Neurotrophins bind two types of receptors, Trk tyrosine kinase receptors and the common p75 receptor.; Disturbances in Trk expression or signaling can lead to certain cancers such as neuroblastomas and melanomas (TrkA responsive) and medulloblastomas (TrkC responsive). Less is known about the role of p75 in cancer as it plays such varying roles and regulatory functions.; We characterized the in vitro and in vivo growth kinetics, tumorigenic potential and response to chemotherapeutics of PC 12-wt rat pheochromocytoma cells and variants expressing varying levels of TrkA or TrkC with or without p75.; We find that independent expression of TrkA or p75 leads to higher growth rates and tumorigenic potential whereas co-expression of Trk with p75 lowers it. Additionally, differential neurotrophin receptor expression leads to different sensitivities to chemotherapeutics. This work will help design therapies for tumors with unique neurotrophin receptor phenotypes. |
