Lo Hui-Wen, Hsu Sheng-Chieh, Ali-Seyed Mohamed, Gunduz Mehmet, Xia Weiya, Wei Yongkun, Bartholomeusz Geoffrey, Shih Jin-Yuan, Hung Mien-Chie
Cancer Cell. 2005 Jun;7(6):575-89. doi: 10.1016/j.ccr.2005.05.007.
Epidermal growth factor receptor (EGFR) exists in the nucleus of highly proliferative cells where it functions as a transcription factor. Although EGFR has transactivational activity, it lacks a DNA binding domain and, therefore, may require a DNA binding transcription cofactor for its transcriptional function. Here, we report that EGFR physically interacts with signal transducers and activators of transcription 3 (STAT3) in the nucleus, leading to transcriptional activation of inducible nitric oxide synthase (iNOS). In breast carcinomas, nuclear EGFR positively correlates with iNOS. This study describes a mode of transcriptional control involving cooperated efforts of STAT3 and nuclear EGFR. Our work suggests that the deregulated iNOS/NO pathway may partly contribute to the malignant biology of tumor cells with high levels of nuclear EGFR and STAT3.
表皮生长因子受体（EGFR）存在于高增殖细胞的细胞核中，在那里它作为一种转录因子发挥作用。尽管EGFR具有反式激活活性，但它缺乏DNA结合结构域，因此，其转录功能可能需要一种DNA结合转录辅因子。在此，我们报告EGFR在细胞核中与信号转导和转录激活因子3（STAT3）发生物理相互作用，导致诱导型一氧化氮合酶（iNOS）的转录激活。在乳腺癌中，细胞核EGFR与iNOS呈正相关。本研究描述了一种涉及STAT3和细胞核EGFR协同作用的转录控制模式。我们的工作表明，失调的iNOS/NO途径可能部分促成了具有高水平细胞核EGFR和STAT3的肿瘤细胞的恶性生物学行为。
