Thomson J A, Leonard J H, McGregor K, Sturm R A, Parsons P G
Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Herston, Australia.
Int J Cancer. 1994 Jul 15;58(2):285-90. doi: 10.1002/ijc.2910580223.
We have established a number of cell lines from Merkel cell carcinoma (MCC) of the skin. In many respects these cell lines resemble those established from small cell lung cancer (SCLC) and it is difficult to differentiate between metastatic MCC and SCLC on morphological or histochemical criteria. Both are thought to be neuroendocrine tumours and may express a number of neuroendocrine markers. SCLC cell lines express the octamer-DNA binding transcription factor brn-2 gene products N-Oct3 and N-Oct5, which are restricted to the neuroectodermal cell lineage. In DNA binding studies using a consensus octamer recognition site we have found that 4 of 8 MCC cell lines examined expressed brn-2 in at least trace amounts compared with 3 SCLC cell lines which all expressed brn-2 proteins at high levels. Moreover, these DNA binding studies were extended by using a high-affinity brn-2 recognition site related to the degenerate octamer TAATGARAT-motif. This identified a novel DNA binding protein in a subset of MCC cell lines. The protein was absent from the three SCLC cell lines, melanoma cells and brain tissue. This binding activity, which we term Merkel cell DNA nuclear (MNF), was shown to be specific by competitive inhibition with oligonucleotide binding sites and was not inhibited by polyclonal antisera against the Oct-1, Oct-2 or Brn-2 proteins. This protein may serve as a unique marker for MCC compared with SCLC cells and may be involved in regulating the Merkel cell phenotype.
我们已经从皮肤默克尔细胞癌（MCC）建立了多个细胞系。在许多方面，这些细胞系类似于从小细胞肺癌（SCLC）建立的细胞系，并且很难根据形态学或组织化学标准区分转移性MCC和SCLC。两者都被认为是神经内分泌肿瘤，可能表达多种神经内分泌标志物。SCLC细胞系表达八聚体-DNA结合转录因子brn-2基因产物N-Oct3和N-Oct5，它们仅限于神经外胚层细胞谱系。在使用共有八聚体识别位点的DNA结合研究中，我们发现，与3个均高水平表达brn-2蛋白的SCLC细胞系相比，所检测的8个MCC细胞系中有4个至少微量表达brn-2。此外，通过使用与简并八聚体TAATGARAT基序相关的高亲和力brn-2识别位点，扩展了这些DNA结合研究。这在一部分MCC细胞系中鉴定出一种新的DNA结合蛋白。在3个SCLC细胞系、黑色素瘤细胞和脑组织中未发现该蛋白。这种结合活性，我们称之为默克尔细胞DNA核蛋白（MNF），通过与寡核苷酸结合位点的竞争性抑制显示具有特异性，并且不受针对Oct-1、Oct-2或Brn-2蛋白的多克隆抗血清的抑制。与SCLC细胞相比，这种蛋白可能作为MCC的独特标志物，并且可能参与调节默克尔细胞表型。
