Rydén M, Sehgal R, Dominici C, Schilling F H, Ibáñez C F, Kogner P
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Br J Cancer. 1996 Sep;74(5):773-9. doi: 10.1038/bjc.1996.435.
Childhood neuroblastoma tumours of the sympathetic nervous system show a remarkable clinical heterogeneity ranging from spontaneous regression to unfavourable outcome despite intensive therapy. Favourable neuroblastomas often express high levels of trkA mRNA, encoding the tyrosine kinase receptor for nerve growth factor. We have investigated mRNA expression for the neurotrophin receptor trkC in 23 primary neuroblastomas using a sensitive RNAase protection assay. TrkC expression was detected in 19 of these tumours at highly variable levels with a 300-fold difference between the highest and lowest values. Significantly higher levels of trkC mRNA were found in tumours from patients with favourable features such as low age (P < 0.012), favourable tumour stage (P < 0.012) and favourable prognosis (P < 0.05). Children with intermediate or high trkC mRNA expression had better prognosis compared with those with low or undetectable levels (83.3% vs 20%, P = 0.005). Further characterisation of trkC mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR) showed that mRNA encoding the full-length cytoplasmic tyrosine kinase domain of the receptor was only expressed in a subset of favourable tumours. These data show that favourable neuroblastomas may express the full trkC receptor while advanced tumours, in particular MYCN-amplified neuroblastoma, seem to either express no trkC or truncated trkC receptors of as yet unknown biological function. These data are suggestive of a role for trkC and its preferred ligand neutotrophin-3, NT-3, in neuroblastoma differentiation and/or regression.
交感神经系统的儿童神经母细胞瘤肿瘤表现出显著的临床异质性，从自发消退到即便接受强化治疗仍预后不良。预后良好的神经母细胞瘤通常高水平表达trkA mRNA，其编码神经生长因子的酪氨酸激酶受体。我们使用灵敏的核糖核酸酶保护试验研究了23例原发性神经母细胞瘤中神经营养因子受体trkC的mRNA表达。在这些肿瘤中的19例检测到了trkC表达，其水平高度可变，最高值与最低值相差300倍。在具有低年龄（P < 0.012）、良好肿瘤分期（P < 0.012）和良好预后（P < 0.05）等良好特征的患者的肿瘤中发现trkC mRNA水平显著更高。与trkC mRNA表达水平低或检测不到的儿童相比，trkC mRNA表达水平中等或高的儿童预后更好（83.3%对20%，P = 0.005）。通过逆转录聚合酶链反应（RT-PCR）对trkC mRNA表达进行的进一步表征表明，编码该受体全长胞质酪氨酸激酶结构域的mRNA仅在一部分预后良好的肿瘤中表达。这些数据表明，预后良好的神经母细胞瘤可能表达完整的trkC受体，而进展期肿瘤，尤其是MYCN扩增的神经母细胞瘤，似乎要么不表达trkC，要么表达生物学功能尚不清楚且截短的trkC受体。这些数据提示trkC及其首选配体神经营养因子-3（NT-3）在神经母细胞瘤分化和/或消退中起作用。
