Lavenius E, Gestblom C, Johansson I, Nånberg E, Påhlman S
Department of Pathology, University of Uppsala, University Hospital, Sweden.
Cell Growth Differ. 1995 Jun;6(6):727-36.
Human neuroblastoma cell lines frequently express the TRK-A proto-oncogene and bind nerve growth factor (NGF) but do not differentiate when exposed to NGF. Transient transfection of an exogenous TRK-A gene into SH-SY5Y and LA-N-5 neuroblastoma cells restored the ability of these tumor cells to differentiate with NGF. Stable TRK-A-transfected SH-SY5Y cell clones were isolated, and they responded to NGF by autophosphorylation of p140trk-A, c-fos induction, morphological differentiation, and increased expression of two neuronal marker genes, neuropeptide tyrosine and GAP-43. In phorbol ester-induced differentiated wild-type cells, TRK-A expression was increased with no change in NGF responsiveness. Thus, the restoration of the NGF-induced differentiation pathway by exogenous TRK-A presents a system of NGF-responsive human cultured cells and focuses attention on the trk-A protein and its function or malfunction in neuroblastoma.
人神经母细胞瘤细胞系经常表达TRK - A原癌基因并结合神经生长因子（NGF），但在暴露于NGF时不会分化。将外源性TRK - A基因瞬时转染到SH - SY5Y和LA - N - 5神经母细胞瘤细胞中，恢复了这些肿瘤细胞与NGF一起分化的能力。分离出稳定转染TRK - A的SH - SY5Y细胞克隆，它们通过p140trk - A的自磷酸化、c - fos诱导、形态分化以及两种神经元标记基因神经肽酪氨酸和GAP - 43表达增加来对NGF作出反应。在佛波酯诱导分化的野生型细胞中，TRK - A表达增加而NGF反应性没有变化。因此，外源性TRK - A恢复NGF诱导的分化途径，提供了一个对NGF有反应的人类培养细胞系统，并将注意力集中在trk - A蛋白及其在神经母细胞瘤中的功能或功能失调上。
