Wazer D E, Liu X L, Chu Q, Gao Q, Band V
Department of Radiation Oncology, New England Medical Center, Boston, MA, USA.
Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3687-91. doi: 10.1073/pnas.92.9.3687.
Multiple mammary epithelial cell (MEC) types are observed both in mammary ducts in vivo and in primary cultures in vitro; however, the oncogenic potential of different cell types remains unknown. Here, we used human papilloma virus 16 E6 and E7 oncogenes, which target p53 and Rb tumor suppressor proteins, respectively, to immortalize MECs present in early or late passages of human mammary tissue-derived cultures or in milk. One MEC subtype was exclusively immortalized by E6; such cells predominated in late-passage cultures but were rare at early passages and apparently absent in milk. Surprisingly, a second cell type, present only in early-passage tissue-derived cultures, was fully immortalized by E7 alone. A third cell type, observed in tissue-derived cultures and in milk, showed a substantial extension of life span with E7 but eventually senesced. Finally, both E6 and E7 were required to fully immortalize milk-derived MECs and a large proportion of MECs in early-passage tissue-derived cultures, suggesting the presence of another discrete subpopulation. Identification of MECs with distinct susceptibilities to p53- and Rb-targeting human papillomavirus oncogenes raises the possibility that these cells may serve as precursors for different forms of breast cancer.
在体内的乳腺导管和体外的原代培养物中均观察到多种乳腺上皮细胞（MEC）类型；然而，不同细胞类型的致癌潜力仍然未知。在这里，我们使用分别靶向p53和Rb肿瘤抑制蛋白的人乳头瘤病毒16 E6和E7癌基因，使存在于人类乳腺组织来源培养物的早期或晚期传代细胞或乳汁中的MEC永生化。一种MEC亚型仅被E6永生化；这类细胞在晚期传代培养物中占主导，但在早期传代时很少见，在乳汁中显然不存在。令人惊讶的是，仅存在于早期传代组织来源培养物中的第二种细胞类型仅被E7完全永生化。在组织来源培养物和乳汁中观察到的第三种细胞类型，其寿命在E7作用下有显著延长，但最终衰老。最后，E6和E7都需要才能使乳汁来源的MEC和早期传代组织来源培养物中的大部分MEC完全永生化，这表明存在另一个离散的亚群。鉴定对靶向p53和Rb的人乳头瘤病毒癌基因具有不同敏感性的MEC，增加了这些细胞可能作为不同形式乳腺癌前体的可能性。
