TrkAIII. A novel hypoxia-regulated alternative TrkA splice variant of potential physiological and pathological importance.
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.
Tacconelli
Antonella
A
Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy.
Farina
Antonietta R
AR
Cappabianca
Lucia
L
Gulino
Alberto
A
Mackay
Andrew R
AR
D017398:Alternative Splicing; D002454:Cell Differentiation / Q000235:genetics; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology; D009432:Neural Crest / Q000166:cytology / Q000502:physiology; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D020917:Receptor, trkA / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics
D004273:DNA, Neoplasm; D020917:Receptor, trkA