van Nie R, Hilgers J
J Natl Cancer Inst. 1976 Jan;56(1):27-32. doi: 10.1093/jnci/56.1.27.
Early stages of mammary tumors (EMT) were induced with a combined treatment of progesterone (P) and estrone (E) in ovariectomized adult GRS/A (GR) mice, a strain of European origin and with a high incidence of mammary cancer. The mammary tumors were comparable to the pregnancy-dependent tumors of breeding females of this strain. The hormone treatment did not lead to EMT in a variety of other strains and only occasionally in the RIII an C3H strains. Treatment with P or E alone di not lead to EMT in GR mice, but treatment with the steroid compound 17 alpha-ethynyl-19-nortestosterone (ANT) did mimic the combined effe(t of P and E. Since EMT could be induced by ANT in all ovariectomized adult GR mice within 3 weeks, this tumor-induction method was suitable for analysis of the gene responsible for palpable, pregnancy-dependent mammary tumors of this strain. Another argument for the usefulness of this test for genetic analysis was the fact that, though mouse mammary tumor virus (MuMTV) of the GR strain was introduced into BALB/c and tmas mice by foster-nursing, ANT treatment did not lead to EMT. First and second backcross analyses showed that one gene was responsible for EMT induction. There was a strong (orrelation between the presence of EMT and MuMTV antigens in the mammary glands and milk of several first backcross populations between GR and other strains such as C57BL, BALB/c, DBAf, and C3Hf. This suggested that the expression of MuMTV antigens was also controlled by the EMT gene. Two types of resistance phenomena were observed. Neither type could prevent EMT after hormone treatment; however, they could delay EMT development. One resistance factor for EMT induction was noticeable and dominant in reciprocal hybrids of the GR and DBAf strains, whereas another resistance factor was detected in the backcross population only [i.e., in the C57BL X (C57BL X Gr) ba(kcross] and not in hybrids; therefore, this factor was recessive. Until now, linkage experiments with 18 markers to locate the gene for EMT induction in the map of the mouse were unsuccessful.
通过对成年去卵巢GRS/A（GR）小鼠（一种欧洲起源且乳腺癌发病率高的品系）联合使用孕酮（P）和雌酮（E）诱导乳腺肿瘤早期阶段（EMT）。这些乳腺肿瘤与该品系繁殖雌性的妊娠依赖性肿瘤相似。激素处理在多种其他品系中未导致EMT，仅偶尔在RIII和C3H品系中出现。单独用P或E处理GR小鼠不会导致EMT，但用类固醇化合物17α-乙炔基-19-去甲睾酮（ANT）处理确实模拟了P和E的联合作用。由于ANT可在3周内诱导所有成年去卵巢GR小鼠发生EMT，这种肿瘤诱导方法适用于分析该品系可触及的妊娠依赖性乳腺肿瘤相关基因。该试验对遗传分析有用的另一个证据是，尽管通过寄养将GR品系的小鼠乳腺肿瘤病毒（MuMTV）引入BALB/c和tmas小鼠，但ANT处理并未导致EMT。首次和第二次回交分析表明，一个基因负责EMT诱导。在GR与其他品系（如C57BL、BALB/c、DBAf和C3Hf）的几个首次回交群体的乳腺和乳汁中，EMT的存在与MuMTV抗原之间存在很强的相关性。这表明MuMTV抗原的表达也受EMT基因控制。观察到两种抗性现象。两种类型都不能在激素处理后阻止EMT；然而，它们可以延迟EMT的发展。一种EMT诱导抗性因子在GR和DBAf品系的 reciprocal 杂种中明显且占主导地位，而另一种抗性因子仅在回交群体中检测到[即，在C57BL X（C57BL X Gr）回交中]，在杂种中未检测到；因此，该因子是隐性的。到目前为止，用18个标记进行连锁实验以在小鼠图谱中定位EMT诱导基因未成功。
