Lindvall Charlotta, Bu Wen, Williams Bart O, Li Yi
Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, MI 49503, USA.
Stem Cell Rev. 2007 Jun;3(2):157-68. doi: 10.1007/s12015-007-0025-3.
The breast epithelium comprises cells at different stages of differentiation, including stem cells, progenitor cells, and more differentiated epithelial and myoepithelial cells. Wnt signaling plays a critical role in regulating stem/progenitor cells in the mammary gland as well as other tissue compartments. Furthermore, there is strong evidence suggesting that aberrant activation of Wnt signaling induces mammary tumors from stem/progenitor cells, and that Wnt exerts its oncogenic effects through LRP5/6-mediated activation of beta-catenin and mTOR pathways. Recent studies using avian retrovirus-mediated introduction of oncogenes into a small subset of somatic mammary cells suggest that polyoma middle T antigen (PyMT) may also preferentially transform stem/progenitor cells. These observations suggest that stem/progenitor cells in the mammary gland may be especially susceptible to oncogenic transformation. Whether more differentiated cells may also be transformed by particular oncogenes is actively debated; it is presently unclear whether stem cells or differentiated mammary cells are more susceptible to transformation by individual oncogenes. Better stem cell and progenitor cell markers as well as the ability to specifically target oncogenes into different mammary cell types will be needed to determine the spectrum of oncogene transformation for stem cells versus more differentiated cells.
乳腺上皮由处于不同分化阶段的细胞组成，包括干细胞、祖细胞以及分化程度更高的上皮细胞和肌上皮细胞。Wnt信号在调节乳腺以及其他组织区室中的干细胞/祖细胞方面发挥着关键作用。此外，有强有力的证据表明，Wnt信号的异常激活会从干细胞/祖细胞诱导产生乳腺肿瘤，并且Wnt通过LRP5/6介导的β-连环蛋白和mTOR通路的激活发挥其致癌作用。最近使用禽逆转录病毒介导将癌基因导入一小部分体细胞性乳腺细胞的研究表明，多瘤病毒中T抗原（PyMT）也可能优先转化干细胞/祖细胞。这些观察结果表明，乳腺中的干细胞/祖细胞可能特别容易发生致癌转化。更分化的细胞是否也可能被特定癌基因转化，目前存在激烈争论；目前尚不清楚干细胞或分化的乳腺细胞是否更容易被单个癌基因转化。需要更好的干细胞和祖细胞标记物以及将癌基因特异性靶向不同乳腺细胞类型的能力，以确定干细胞与更分化细胞的癌基因转化谱。
