Lucchini F, Sacco M G, Hu N, Villa A, Brown J, Cesano L, Mangiarini L, Rindi G, Kindl S, Sessa F
Environment Institute-Life Sciences, Joint Research Centre, Ispra, Varese, Italy.
Cancer Lett. 1992 Jul 10;64(3):203-9. doi: 10.1016/0304-3835(92)90044-v.
Transgenic mice carrying various oncogenes driven by mammary gland specific enhancers develop mammary tumors usually arising in a stochastic way. The only exception is a mouse lineage (TG.NF) carrying an activated rat Neu oncogene driven by the murine mammary tumor virus long terminal repeat (MMTV-LTR) that gave rise to rapid and multifocal mammary tumors interpreted as a result of a single-step neoplastic transformation. The effect of the oncogene appeared to be specific for breast tissue, since salivary and Harderian glands as well as epididymis expressed high levels of Neu but only developed hyperplasia (Muller et al., Cell, (1988) 54, p. 105). Here we describe a transgenic mouse lineage for the MMTV-Neu, analysed up to third generation. Multifocal tumors involving mammary glands arose very rapidly in all females independently from pregnancy and in some males. Moreover, multifocal neoplasias occurred also in salivary and Harderian glands and in the epididymis at a very high rate. These data demonstrate that the Neu oncogene can induce tumors in all the tissues where it is expressed at high levels.
携带由乳腺特异性增强子驱动的各种癌基因的转基因小鼠通常会随机发生乳腺肿瘤。唯一的例外是一个小鼠品系（TG.NF），它携带由鼠乳腺肿瘤病毒长末端重复序列（MMTV-LTR）驱动的激活型大鼠Neu癌基因，该品系会引发快速且多灶性的乳腺肿瘤，这被解释为单步肿瘤转化的结果。癌基因的作用似乎对乳腺组织具有特异性，因为唾液腺、哈德氏腺以及附睾中Neu的表达水平很高，但仅出现了增生（Muller等人，《细胞》，（1988年）54卷，第105页）。在此，我们描述了一个MMTV-Neu转基因小鼠品系，并对其进行了三代分析。在所有雌性小鼠中，无论是否怀孕，以及在一些雄性小鼠中，多灶性乳腺肿瘤都迅速出现。此外，唾液腺、哈德氏腺和附睾中也以很高的发生率出现多灶性肿瘤。这些数据表明，Neu癌基因能够在其高表达的所有组织中诱导肿瘤发生。
