Band V
Department of Radiation Oncology, New England Medical Center, Boston, MA, USA.
Semin Cancer Biol. 1995 Jun;6(3):185-92. doi: 10.1006/scbi.1995.0015.
Recent in-vitro models of mammary epithelial cell (MEC) immortalization have provided a practical approach to begin to dissect the molecular mechanisms of breast tumorigenesis. Introduction of a single oncogene, the human papilloma virus (HPV)-16 E6, induces efficient and reproducible preneoplastic transformation of normal MECs, by inducing degradation of the tumor suppressor protein p53. The role of p53 has also been demonstrated by analyses of a model of gamma-radiation-induced MEC transformation. Recently, efficient retroviral gene transfer has allowed identification of multiple mammary epithelial cell types that show distinct susceptibilities to HPV E6 and E7 oncogenes, indicating a cell-type-specific predominance of the tumor suppressor proteins p53 and Rb which are targeted by E6 and E7, respectively. Further analyses of these models are likely to elucidate the biochemical mechanisms of early mammary tumorigenesis.
近期乳腺上皮细胞（MEC）永生化的体外模型为深入研究乳腺肿瘤发生的分子机制提供了一种实用方法。引入单个癌基因——人乳头瘤病毒（HPV）-16 E6，通过诱导肿瘤抑制蛋白p53降解，可高效且可重复地诱导正常MEC发生肿瘤前转化。通过对γ射线诱导的MEC转化模型的分析，也证实了p53的作用。最近，高效的逆转录病毒基因转移使得能够鉴定出多种对HPV E6和E7癌基因具有不同易感性的乳腺上皮细胞类型，这表明分别被E6和E7靶向的肿瘤抑制蛋白p53和Rb在细胞类型上具有特异性优势。对这些模型的进一步分析可能会阐明早期乳腺肿瘤发生的生化机制。
