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尿皮质素通过 CRF 受体 1 刺激 ERK1/2 信号通路和 HeLa 细胞的增殖。

Urocortin stimulates the ERK1/2 signaling pathway and the proliferation of HeLa cells via CRF receptor 1.

机构信息

Department of Medical Biology and Central Electron Microscope Laboratory, Medical School, University of Pécs, Hungary.

Signal Transduction Research Group, János Szentágothai Research Centre, Pécs, Hungary.

出版信息

FEBS Open Bio. 2023 May;13(5):818-832. doi: 10.1002/2211-5463.13602. Epub 2023 Apr 2.

DOI:10.1002/2211-5463.13602
PMID:36971048
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10153344/
Abstract

Corticotropin-releasing factor (CRF) stimulates adrenocorticotropic hormone (ACTH) secretion from the pituitary gland and is an essential regulator of the hypothalamic-pituitary-adrenocortical axis. Isoforms of CRF receptor are known to mediate the effects of urocortin stress ligands on the regulation of stress responses, anxiety, and feeding behavior; however, urocortin stress ligands also influence cell proliferation. In view of the tumor-promoting capacity of prolonged stress, here we investigated (a) the effect of urocortin on cell proliferative signaling via extracellular signal-regulated kinase 1/2, (b) the expression and cellular distribution of the specific CRF receptor isoforms, and (c) the intracellular localization of phosphorylated ERK1/2 in HeLa cells. Stimulation of cell proliferation was observed in the presence of 10 nm urocortin. Our data also suggest that MAP kinase MEK, the transcription factors E2F-1 and p53, and PKB/Akt are involved in this process. These findings may have therapeutic relevance for the targeted treatment of various malignancies.

摘要

促肾上腺皮质激素释放因子（CRF）刺激垂体分泌促肾上腺皮质激素（ACTH），是下丘脑-垂体-肾上腺皮质轴的重要调节因子。已知 CRF 受体的同工型介导尿皮质素应激配体对调节应激反应、焦虑和摄食行为的影响；然而，尿皮质素应激配体也影响细胞增殖。鉴于长期应激具有促进肿瘤的能力，我们在此研究了（a）尿皮质素通过细胞外信号调节激酶 1/2 对细胞增殖信号的影响，（b）特定 CRF 受体同工型的表达和细胞分布，以及（c）磷酸化 ERK1/2 在 HeLa 细胞中的细胞内定位。在存在 10nm 尿皮质素的情况下观察到细胞增殖的刺激。我们的数据还表明，MAP 激酶 MEK、转录因子 E2F-1 和 p53 以及 PKB/Akt 参与了这一过程。这些发现可能对各种恶性肿瘤的靶向治疗具有重要意义。

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