相关实验视频

Updated: Jun 30, 2025

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

蛋白质基因分析显示,ESR1突变增强了循环林依赖性激酶信号传递

Tommaso De Marchi¹, Chun-Fui Lai², Georgia M Simmons²

¹Division of Surgery, Oncology, and Pathology, Department of Clinical Sciences, Lund University, Solvegatan 19, 22362, Lund, Sweden. tommaso.de_marchi@med.lu.se.

Scientific reports

|March 23, 2024

概括

乳腺癌中的雌激素受体 (ER) 突变驱动了扩散和对内分泌治疗的耐药性. 这项研究揭示了ER突变细胞的蛋白质变化,包括免疫信号通路的丰富,证实了它们的雌激素独立生长.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
蛋白质组学是指蛋白质组学.

背景情况:

雌激素受体 (ER,ESR1基因) 是75%的乳腺癌的关键驱动因素,由内分泌疗法准.
ESR1突变与转移性乳腺癌的治疗耐药性有关,特别是对芳酶抑制剂的耐药性.
虽然研究了遗传和转录基因变异,但ER突变体中的蛋白质水平变化仍未得到充分研究.

研究的目的:

研究乳腺癌细胞系中常见ESR1突变 (Y537N,Y537S) 的蛋白质和蛋白质变异.
描述ER突变细胞与野生型 (wt) ER细胞的蛋白质中心差异.
了解ER突变乳腺癌中雌激素独立扩散的机制.

主要方法:

利用基于集成质谱的蛋白质组学方法.
分析了ER突变和wt ER乳腺癌细胞系的全球蛋白质组和蛋白质组概况.
综合蛋白质和蛋白质数据,以确定特定路径的变化.

主要成果:

ER突变细胞显示了线粒体和免疫信号通路的丰富.
蛋白质组分析显示,增殖相关激酶的活性增加,包括CDK和mTOR.
在突变细胞和Wt ER细胞之间观察到运动和增殖的途径依赖差异.
蛋白质和酸化模式证实了ER突变细胞的雌激素独立表型.
在ESR1突变模型中,发现免疫信号通路在蛋白质层面上被丰富.

结论:

这是对ESR1突变乳腺癌模型的第一个以蛋白质为中心的表征.
证实了ER突变乳腺癌细胞的雌激素独立生长.
揭示了ER突变细胞在蛋白质层面上显著丰富免疫信号通路.

更多相关视频

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline

Published on: November 29, 2016

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

相关概念视频

mTOR Signaling and Cancer Progression

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...

MAPK Signaling Cascades

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...