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通过雌激素受体-PAX2对ERBB2的调节决定了对他莫西芬的反应
Antoni Hurtado1, Kelly A Holmes, Timothy R Geistlinger
1Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Nature
|November 14, 2008
概括
雌激素受体 (ER) 和他莫西芬复合体通过一个cis调节元件直接抑制ERBB2转录. 蛋白质PAX2调解这种抑制,影响乳腺癌中塔莫西芬的反应.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 雌激素受体 (ER) 和ERBB2 / HER-2通路之间的交叉涉及乳腺癌.
- 这些途径之间还没有建立直接的转录连接.
研究的目的:
- 为了阐明ERBB2通过ER和他莫西芬的直接转录调节.
- 确定ER-ERBB2路径交叉中的关键介质,与乳腺癌治疗反应相关.
主要方法:
- 在人类细胞系中分析ERBB2转录.
- 调查配对盒2基因产物 (PAX2) 作为调解者的作用.
- 评估PAX2和AIB-1/SRC-3之间在ERBB2转录调节方面的竞争.
主要成果:
- 雌激素-ER和他莫西芬-ER复合体通过特定基因的cis-regulatory元素直接抑制ERBB2转录.
- PAX2 作为 ER 和他莫西芬诱导的 ERBB2 抑制的关键调解者.
- PAX2 和 ER 联合激活剂 AIB-1/SRC-3 在 ERBB2 调节方面竞争,决定着他莫西芬的反应.
结论:
- ER-PAX2相互作用提供了ER-阳性和ERBB2-阳性乳腺癌亚型之间的机械联系.
- 这一途径表明了ER阳性瘤向侵袭性ERBB2阳性瘤的进展机制.
- 这些发现提供了对乳腺癌内分泌抵抗的洞察.
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