尽管乳腺癌的治疗已经取得了重大进展，但如果能够从一开始就阻止乳腺癌的发展，就不需要毒性疗法。虽然由于疾病潜伏期长和癌症发展随机性，乳腺癌预防很难在人类身上进行研究，但发病率 100% 且明确乳腺肿瘤发病的转基因小鼠模型为肿瘤预防研究提供了极好的模型。在这项研究中，我们使用 Neu/Erbb2 转基因小鼠 (MTB-TAN) 作为人类 HER2 乳腺癌模型，以研究称为 miR-200 家族的 microRNA 家族是否可以预防乳腺肿瘤的发展。 Neu 过度表达在 Neu 过度表达的 38 天内诱导 100% 的小鼠出现明显的乳腺肿瘤。当miR-200b/200a/429簇与Neu在相同乳腺上皮细胞（MTB-TANba429小鼠）中共过表达时，miR-200b/200a/429簇阻止Neu诱导乳腺上皮增生和乳腺肿瘤发展。 RNA测序揭示了Neu转基因小鼠乳腺细胞外基质的改变以及包括肌上皮细胞在内的基质细胞的减少。平滑肌肌动蛋白的免疫组织化学证实，对照和MTB-TANba429小鼠的乳腺上皮细胞被一层肌上皮细胞包围，并且这些肌上皮细胞在增生的MTB-TAN小鼠中丢失。因此，我们首次证明，乳腺上皮细胞中 miR-200 家族成员的表达升高可以通过调节肌上皮细胞来完全阻止 Neu 转基因小鼠的乳腺肿瘤发展。© 2024 作者。约翰·威利出版的《国际癌症杂志》

Although significant progress in the treatment of breast cancer has been achieved, toxic therapies would not be required if breast cancer could be prevented from developing in the first place. While breast cancer prevention is difficult to study in humans due to long disease latency and stochastic cancer development, transgenic mouse models with 100% incidence and defined mammary tumor onset, provide excellent models for tumor prevention studies. In this study, we used Neu/Erbb2 transgenic mice (MTB-TAN) as a model of human HER2+ breast cancer to investigate whether a family of microRNAs, known as the miR-200 family, can prevent mammary tumor development. Overexpression of Neu induced palpable mammary tumors in 100% of the mice within 38 days of Neu overexpression. When the miR-200b/200a/429 cluster was co-overexpressed with Neu in the same mammary epithelial cells (MTB-TANba429 mice), the miR-200b/200a/429 cluster prevented Neu from inducing mammary epithelial hyperplasia and mammary tumor development. RNA sequencing revealed alterations in the extracellular matrix of the mammary gland and a decrease in stromal cells including myoepithelial cells in Neu transgenic mice. Immunohistochemistry for smooth muscle actin confirmed that mammary epithelial cells in control and MTB-TANba429 mice were surrounded by a layer of myoepithelial cells and these myoepithelial cells were lost in MTB-TAN mice with hyperplasia. Thus, we have shown for the first time that elevated expression of miR-200 family members in mammary epithelial cells can completely prevent mammary tumor development in Neu transgenic mice possibly through regulating myoepithelial cells.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.