Determination of the mammary epithelial cell that serves as the cell of origin for breast cancer is key to understand tumor heterogeneity and clinical management. In this study, we aimed to decipher whether Rank expression in the presence of PyMT and Neu oncogenes might affect the cell of origin of mammary gland tumors. We observed that Rank expression in PyMT^+/− and Neu^+/− mammary glands alters the basal and luminal mammary cell populations already in preneoplasic tissue, which may interfere with the tumor cell of origin restricting their tumorigenesis ability upon transplantation assays. In spite of this, Rank expression eventually promotes tumor aggressiveness once tumorigenesis is established.

确定作为乳腺癌起源细胞的乳腺上皮细胞是了解肿瘤异质性和临床治疗的关键。在本研究中，我们旨在破译 PyMT 和 Neu 癌基因存在下的 Rank 表达是否可能影响乳腺肿瘤的细胞起源。我们观察到 PyMT ^+/-和 Neu ^+/-乳腺中的 Rank 表达改变了肿瘤前组织中已有的基底和管腔乳腺细胞群，这可能会干扰肿瘤细胞来源，限制其在移植试验中的肿瘤发生能力。尽管如此，一旦肿瘤发生确立，Rank 表达最终会促进肿瘤的侵袭性。