乳腺癌中的雌激素受体（ER）在进展和治疗过程中可能发生变化，但其机制尚未得到充分研究。本研究成功地从33例乳腺癌患者的样本中制备出器官样体，并研究了它们的ER表达情况。原始器官样体中ER的表达状态良好保持，但在大部分情况下，经过传代后其表达水平下降。事实上，研究的器官样体系列被分为保持高水平ER表达的（9%），完全丧失ER表达的（9%），以及具有不同程度抑制ER表达的（82%）。在某些情况下，经过传代后ER表达会突然明显下降。标记蛋白免疫组化显示，经过传代后，分化状态从乳腺上皮-乳腺基底样转化。差异表达基因提示，传代的器官样体中NOTCH信号通路被激活，而NOTCH抑制剂能够显著恢复降低的ER表达并改变分化状态。我们的发现表明，乳腺癌的乳腺上皮型癌细胞的分化状态具有一定的灵活性，并且通过抑制NOTCH信号通路，我们可以保持乳腺上皮型乳腺癌器官样体的分化状态。© 2023年作者（s）独家许可给日本人类细胞学会。

Estrogen receptor (ER) expression in breast cancer can change during progression and the treatment, but the mechanism has not been well studied. In this study, we successfully prepared organoids from samples obtained from 33 luminal-type breast cancer patients and studied their ER expression. The expression status was well maintained in primary organoids, whereas it decreased after passaging in most of the cases. In fact, the studied organoid lines were classified into those that retained a high level of ER expression (9%), those that completely lost it (9%), and those that repressed it to varying degrees (82%). In some cases, the ER expression was suddenly and drastically decreased after passaging. Marker protein immunohistochemistry revealed that after passaging, the differentiation status shifted from a luminal- to a basal-like status. Differentially expressed genes suggested the activation of NOTCH signaling in the passaged organoids, wherein a NOTCH inhibitor was able to substantially rescue the decreased ER expression and alter the differentiation status. Our findings suggest that the differentiation status of luminal-type cancer cells is quite flexible, and that by inhibiting the NOTCH signaling we can preserve the differentiation status of luminal-type breast cancer organoids.© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.