Abstract

POU2F1 (Oct-1) is a transcription factor, the overexpression of which is found in many human malignant tumors; a significant increase in its level in cells determines the malignant potential of the tumor. POU2F1 is represented in cells by several isoforms that are transcribed from alternative promoters. In Burkitt’s B-cell lymphoma Namalwa, the concentration of tissue-specific isoform Oct-1L is several times higher than in normal B cells. We tested the potential to inhibit the transcription of individual Oct-1 isoforms using the GSK3 kinase inhibitor CHIR, an aminopyrimidine derivative. We have shown that CHIR specifically affects the expression of the tissue-specific isoform Oct-1L, significantly reducing the level of mRNA and Oct-1L protein. However, CHIR does not change the amount of mRNA and protein of the ubiquitous isoform Oct-1A in Namalwa tumor cells. The results obtained show that it is possible to develop a system for selective inhibition of Oct-1 transcription factor isoforms in human cells to suppress drug resistance of tumor cells with a high POU2F1 content.

中文翻译：

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GSK3激酶抑制剂，CHIR，抑制Burkitt Namalwa淋巴瘤细胞中组织特异性POU2F1亚型的转录

摘要

POU2F1（Oct-1）是一种转录因子，在许多人类恶性肿瘤中都有过表达。其细胞水平的显着增加决定了肿瘤的恶性潜能。POU2F1在细胞中由从其他启动子转录的几种同工型表示。在伯基特的B细胞淋巴瘤Namalwa中，组织特异性同工型Oct-1L的浓度是正常B细胞​​的几倍。我们使用GSK3激酶抑制剂CHIR（一种氨基嘧啶衍生物）测试了抑制单个Oct-1亚型转录的潜力。我们已经表明，CHIR特异性影响组织特异性同工型Oct-1L的表达，从而显着降低mRNA和Oct-1L蛋白的水平。然而，CHIR不会改变Namalwa肿瘤细胞中普遍存在的亚型Oct-1A的mRNA和蛋白质的量。获得的结果表明，有可能开发一种选择性抑制人细胞中的Oct-1转录因子同工型的系统，以抑制具有高POU2F1含量的肿瘤细胞的耐药性。