Holloway Kimberly R, Sinha Vidya C, Toneff Michael J, Bu Wen, Hilsenbeck Susan G, Li Yi
Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, United States of America.
Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, United States of America; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States of America.
PLoS One. 2015 Jan 30;10(1):e0117239. doi: 10.1371/journal.pone.0117239. eCollection 2015.
While most breast cancers are thought to arise from the luminal layer of the breast tissue, it remains unclear which specific cells in the luminal layer are the cells of origin of breast cancer. We have previously reported that WAP-positive luminal epithelial cells are at increased susceptibility to tumor initiation by ErbB2 compared to the bulk population, while the mammary cells with canonical Wnt signaling activity fail to evolve into tumors upon ErbB2 activation. Here, we used retrovirus to introduce ErbB2 into the Krt6a-positive mammary progenitor subset of the luminal epithelium and, for comparison, into the mammary luminal epithelium indiscriminately. Tumors developed from both groups of cells with a similar latency. These data indicate that the Krt6a-positive subset of mammary epithelial cells can be induced to form cancer by ErbB2 but it is not more susceptible to tumorigenesis initiated by ErbB2 than the bulk population of the luminal epithelium.
虽然大多数乳腺癌被认为起源于乳腺组织的管腔层，但管腔层中哪些特定细胞是乳腺癌的起源细胞仍不清楚。我们之前报道过，与总体细胞相比，WAP阳性的管腔上皮细胞对ErbB2诱导肿瘤发生的敏感性增加，而具有典型Wnt信号活性的乳腺细胞在ErbB2激活后不会演变成肿瘤。在这里，我们使用逆转录病毒将ErbB2分别导入管腔上皮中Krt6a阳性的乳腺祖细胞亚群，以及作为对照，不加区分地导入乳腺管腔上皮。两组细胞形成肿瘤的潜伏期相似。这些数据表明，乳腺上皮细胞中Krt6a阳性亚群可被ErbB2诱导形成癌症，但它对ErbB2引发的肿瘤发生并不比管腔上皮总体细胞更敏感。
