Recent advances in histogenesis research of lung neuroendocrine cancers: Evidence obtained from functional analyses of primitive neural/neuroendocrine cell-specific transcription factors
Recent advances in histogenesis research of lung neuroendocrine cancers: Evidence obtained from functional analyses of primitive neural/neuroendocrine cell-specific transcription factors
复制标题
肺神经内分泌癌组织发生研究的最新进展：原始神经/神经内分泌细胞特异性转录因子功能分析的证据
作者：
Uchiyama M;Tojo K;Yazawa T;Ota S;Goto T;Kurahashi K;Yazawa T
小细胞癌（SmCC）和大细胞神经内分泌癌（LENEC）被归类为肺的神经内分泌癌（NEC），并且具有极差的扩散性。缺乏针对SmCC和LCNEC的有效治疗策略是一个严重的问题。由于细胞表型的调节是复杂的各种转录因子的作用，研究神经/神经内分泌细胞特异性转录因子的功能对于阐明SmCC和LCNEC的细胞特征和组织发生以及建立针对它们的创新治疗策略非常重要。本文就在肺内皮细胞中特异性高表达的ASCL 1、NeuroD 1、REST、TTF 1和III/IV类POU的功能作一综述。这些转录因子反式激活和/或反式抑制各种基因，并参与神经祖细胞表型、神经内分泌和干细胞标志物表达以及上皮向间充质转化。基于某些类癌表达ASCL 1，NeuroD 1，TTF 1和III/IV类POU以及肺NEC可以从非NE细胞/非NEC细胞发展的证据，讨论了肺NEC，类癌肿瘤和非NEC之间的关系。最后，鉴于原始神经/神经内分泌细胞特异性转录因子表达的相似性，提出了肺NEC组织发生的模型。
Small cell carcinoma (SmCC) and large cell neuroendocrine carcinoma (LENEC) are categorized as neuroendocrine cancers (NECs) of the lung and have extremely poor prognoses. The lack of an effective therapeutic strategy against SmCC and LCNEC is a serious issue. Because the regulation of the cellular phenotype is complicated by the actions of various transcription factors, investigations into the function of neural/neuroendocrine cell‐specific transcription factors are important for elucidating the cellular characteristics and histogenesis of SmCC and LCNEC and for establishing innovative therapeutic strategies against them. In this review, the functions of ASCL1, NeuroD1, REST, TTF1, and class III/IV POU, that are specifically and highly expressed in lung NECs, are introduced. These transcription factors transactivate and/or transrepress various genes and are involved in neural progenitor phenotyping, neuroendocrine and stem cell marker expression, and epithelial‐to‐mesenchymal transition. Based on the evidence that certain carcinoids express ASCL1, NeuroD1, TTF1, and class III/IV POU and that lung NECs can develop from non‐NE cells/non‐NEC cells, the relationships among lung NECs, carcinoid tumors, and non‐NECs are discussed. Finally, a model of the histogenesis of lung NECs in view of similarities in the expression of primitive neural/neuroendocrine cell‐specific transcription factors is proposed.