SIRT1调解乳腺癌的发展和由雌激素相关受体β控制的瘤发生
Monalisa Parija1,2, Surya Prakash1,2, B Madhu Krishna3
1Cancer Biology Lab, Gene Function and Regulation Group, Institute of Life Sciences, Nalco Square, Nadankanan Road, Kalinga Hospital Cross, Chandrasekharpur, Bhubaneswar, Odisha, 751023, India.
Breast cancer (Tokyo, Japan)
|February 29, 2024
概括
与雌激素相关的受体β (ERRβ) 上调 静音交配类型信息调控2同类1 (SIRT1) 在ER阳性乳腺癌中. 这种SIRT1活性促进瘤生长,表明SIRT1抑制剂是潜在的治疗方法.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 沉默交配类型信息调节2同类型1 (SIRT1) 是一种依赖NAD+的基因组脱乙酶,对细胞存活和新陈代谢至关重要.
- 在包括乳腺癌在内的各种癌症中,SIRT1过度表达,并且与雌激素受体α (ERα) 活性有关.
- 与雌激素相关的受体 (ERR) 与ER共享同质性,表明潜在的共享目标基因.
研究的目的:
- 调查雌激素相关受体β (ERRβ) 在调节乳腺癌进展期间沉默交配类型信息调节2同位素1 (SIRT1) 活性中的作用.
- 阐明ERRβ和SIRT1在ER阳性乳腺癌中的功能关系.
主要方法:
- 对SIRT1的5'上游区域进行分析,以确定潜在的雌激素相关反应元件 (ERRE位点).
- 在体外和体内实验验验证ERRE部位并评估SIRT1表达.
- 在ER-阳性乳腺癌细胞中对ERRβ和PCAF的过度表达研究,以评估对SIRT1活性的影响.
主要成果:
- 在ER阳性乳腺癌细胞和组织中,SIRT1的表达显著增强.
- 在SIRT1 5'上游区域确定并验证了6个潜在的ERRE地点.
- 发现SIRT1在ERRβ过度表达的ER-阳性乳腺癌细胞中被上调调节,ERRβ/PCAF联合表达增加了SIRT1活性.
- SIRT1通过促进细胞增殖,迁移和殖民地形成,证明了瘤发生作用.
结论:
- 与雌激素相关的受体β (ERRβ) 在上调调节中发挥着重要作用.在ER阳性乳腺癌中,静音交配类型信息调节2同类1 (SIRT1).
- 通过参与细胞增殖,迁移和殖民地形成,SIRT1有助于乳腺癌的进展.
- SIRT1抑制剂代表了乳腺癌治疗的潜在治疗策略.
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