4-Hydroxytamoxifen作为雌激素受体拮抗剂的基因调控机制
4-Hydroxytamoxifen（4-OHT，AbMole，M10252）是一种选择性雌激素受体调节剂（SERM），在研究中主要作为雌激素受体拮抗剂发挥作用，其作用机制涉及抑制雌激素受体活性并影响转录因子的招募[1, 2]。4-Hydroxytamoxifen在细胞实验中，常用于人乳腺癌细胞系（如MCF-7、MDA-MB 231、T-47D）的研究，例如通过浓度梯度诱导细胞以（100-1000 nM）建立耐药细胞模型（如MCF-7-TamR）[3]。4-Hydroxytamoxifen在MCF-7细胞中，可显著抑制细胞增殖并调控凋亡相关基因的表达[3]。4-Hydroxytamoxifen（ CAS No.：68047-06-3）在分子与细胞生物学中还是一种可以调控外源基因表达的常用化合物，例如4-Hydroxytamoxifen通过激活CreER-T2酶，介导loxP位点特异性重组，实现外源基因在转基因小鼠模型中的条件性敲除或表达。
在动物实验中，4-Hydroxytamoxifen通过腹腔注射用于双转基因Cspg4-cre/Esr1/ROSA26Sortm14(CAG-tdTomato)小鼠模型，诱导重组并触发红色荧光蛋白表达[4]。4-Hydroxytamoxifen还可用于动物肿瘤模型和某些病毒模型，常见于小鼠实验。例如4-Hydroxytamoxifen（4-OHT，AbMole，M10252）在异种移植或同种移植肿瘤模型中，被用于评估抗肿瘤效果。在VSV（水疱性口炎病毒）模型中，4-Hydroxytamoxifen作为小分子诱导剂，可激活Intein剪接以调节病毒复制[5]。
参考文献及鸣谢
[1] Shtaiwi, A.; Adnan, R.; Khairuddean, M.; et al. Computational investigations of the binding mechanism of novel benzophenone imine inhibitors for the treatment of breast cancer. RSC advances 2019, 9 (61), 35401-35416.
[2] Somsen, B. A.; Sijbesma, E.; Leysen, S.; et al. Molecular basis and dual ligand regulation of tetrameric estrogen receptor alpha/14-3-3zeta protein complex. The Journal of biological chemistry 2023, 299 (7), 104855.
[3] Cheng, S.; Castillo, V.; Welty, M.; et al. BreastDefend enhances effect of tamoxifen in estrogen receptor-positive human breast cancer in vitro and in vivo. BMC complementary and alternative medicine 2017, 17 (1), 115.
[4] Valny, M.; Honsa, P.; Kirdajova, D.; et al. Tamoxifen in the Mouse Brain: Implications for Fate-Mapping Studies Using the Tamoxifen-Inducible Cre-loxP System. Frontiers in cellular neuroscience 2016, 10, 243.
[5] Zhao, Z.; Wang, B.; Wu, S.; et al. Regulated control of virus replication by 4-hydroxytamoxifen-induced splicing. Frontiers in microbiology 2023, 14, 1112580.
在动物实验中，4-Hydroxytamoxifen通过腹腔注射用于双转基因Cspg4-cre/Esr1/ROSA26Sortm14(CAG-tdTomato)小鼠模型，诱导重组并触发红色荧光蛋白表达[4]。4-Hydroxytamoxifen还可用于动物肿瘤模型和某些病毒模型，常见于小鼠实验。例如4-Hydroxytamoxifen（4-OHT，AbMole，M10252）在异种移植或同种移植肿瘤模型中，被用于评估抗肿瘤效果。在VSV（水疱性口炎病毒）模型中，4-Hydroxytamoxifen作为小分子诱导剂，可激活Intein剪接以调节病毒复制[5]。
参考文献及鸣谢
[1] Shtaiwi, A.; Adnan, R.; Khairuddean, M.; et al. Computational investigations of the binding mechanism of novel benzophenone imine inhibitors for the treatment of breast cancer. RSC advances 2019, 9 (61), 35401-35416.
[2] Somsen, B. A.; Sijbesma, E.; Leysen, S.; et al. Molecular basis and dual ligand regulation of tetrameric estrogen receptor alpha/14-3-3zeta protein complex. The Journal of biological chemistry 2023, 299 (7), 104855.
[3] Cheng, S.; Castillo, V.; Welty, M.; et al. BreastDefend enhances effect of tamoxifen in estrogen receptor-positive human breast cancer in vitro and in vivo. BMC complementary and alternative medicine 2017, 17 (1), 115.
[4] Valny, M.; Honsa, P.; Kirdajova, D.; et al. Tamoxifen in the Mouse Brain: Implications for Fate-Mapping Studies Using the Tamoxifen-Inducible Cre-loxP System. Frontiers in cellular neuroscience 2016, 10, 243.
[5] Zhao, Z.; Wang, B.; Wu, S.; et al. Regulated control of virus replication by 4-hydroxytamoxifen-induced splicing. Frontiers in microbiology 2023, 14, 1112580.
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乳腺癌
