TY - JOUR
T1 - TrkAIII
T2 - A novel hypoxia-regulated alternative TrkA splice variant of potential physiological and pathological importance
AU - Tacconelli, Antonella
AU - Farina, Antonietta R.
AU - Cappabianca, Lucia
AU - Gulino, Alberto
AU - Mackay, Andrew R.
PY - 2005/1
Y1 - 2005/1
N2 - Nerve growth factor receptor TrkA is critical for development and maturation of central and peripheral nervous systems, regulating proliferation, differentiation and apoptosis. In cancer, TrkA frequently exhibits suppressor activity in nonmutated form and oncogenic activity upon mutation. Our identification of a novel hypoxia-regulated alternative TrkAIII splice variant, expressed by neural crest-derived neuroblastic tumors, that exhibits neuroblastoma tumor promoting activity, adds significantly to our understanding of potential TrkA involvement in cancer. Our observation that hypoxia, which characterizes the tumor micro-environment, stimulates alternative TrkAIII splicing, provides a way by which TrkA tumor suppressing signals may convert to tumor promoting signals during progression and is consistent with conservation and pathological subversion by neural crest-derived neuroblastic tumors of a mechanism of potential physiological importance to normal neural stem/neural crest progenitors.
AB - Nerve growth factor receptor TrkA is critical for development and maturation of central and peripheral nervous systems, regulating proliferation, differentiation and apoptosis. In cancer, TrkA frequently exhibits suppressor activity in nonmutated form and oncogenic activity upon mutation. Our identification of a novel hypoxia-regulated alternative TrkAIII splice variant, expressed by neural crest-derived neuroblastic tumors, that exhibits neuroblastoma tumor promoting activity, adds significantly to our understanding of potential TrkA involvement in cancer. Our observation that hypoxia, which characterizes the tumor micro-environment, stimulates alternative TrkAIII splicing, provides a way by which TrkA tumor suppressing signals may convert to tumor promoting signals during progression and is consistent with conservation and pathological subversion by neural crest-derived neuroblastic tumors of a mechanism of potential physiological importance to normal neural stem/neural crest progenitors.
KW - Hypoxia
KW - Neuroblastoma neural stem cells
KW - Splice variation
KW - TrkA
KW - Tumor progression
UR - http://www.scopus.com/inward/record.url?scp=22844451845&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=22844451845&partnerID=8YFLogxK
M3 - Article
C2 - 15611661
AN - SCOPUS:22844451845
VL - 4
SP - 8
EP - 9
JO - Cell Cycle
JF - Cell Cycle
SN - 1538-4101
IS - 1
ER -