津白Ⅰ和津白Ⅱ杂交小鼠自发性乳腺癌发生及相关机制研究

Spontaneous Breast Cancer in F1 Hybrids of TA Ⅰ and TA Ⅱ Mice and the Underlying Mechanisms

目的:观察津白Ⅰ和津白Ⅱ小鼠杂交后的杂交一代自发性乳腺癌发生,分析父系遗传和母系遗传在TA1和TAⅡ自发性乳腺癌小鼠发生过程中的作用及初步探讨其机制。方法:TAⅠ雄性小鼠和TAⅡ雌性小鼠杂交,TAⅠ雌性小鼠和TAⅡ雄性小鼠杂交,产生的杂交一代分别命名为F1代和F1’代,再各自交配,记录杂交一代雌鼠发瘤情况,并与TAⅡ自发性乳腺癌相比较。结果:9只F1代雌鼠中有8只发瘤,平均发瘤时间为201天,发瘤时平均生产7.67次;8只F1’代雌鼠中有3只发瘤,平均发瘤时间为190天,发瘤时平均生产5.67次。F1代自发瘤发瘤时间明显短于F1’代和TAⅡ自发性乳腺癌小鼠(P<0.05)。结论:母系遗传在TAⅡ自发性乳腺癌发生过程中可能具有重要的作用,F1和F1’小鼠自发性乳腺癌发生时间比TAⅡ小鼠明显缩短。Rb基因突变可能是引起TAⅡ自发性乳腺癌发生的一个较为重要原因。

Objective： To observe the tumorigenesis of spontaneous breast cancer in F1 hybrids of TA Ⅰ and TA Ⅱ mice and to investigate the underlying mechanism. Methods： The hybrids of female TA Ⅱ and male TA Ⅰ were named F1 and the hybrids of female TA Ⅰ and male TA Ⅱ were named F1＇. The F1 and F1＇ hybrids were observed for tumorigenesis. PCNA, Ki-67, P53 and Rb were detected by immunohistoehemistry. Results： Eight of the 9 F1 females were found with spontaneous breast cancer and it was 201 days on average before the cancer was observed. The average parity was 7.67. Three of the 8 F1＇ females were found with spontaneous breast cancer and it was 190 days on average before the cancer was observed. The average parity was 7.67. The spontaneous breast cancer was identified as adenocarcinoma by pathology. Immunohistochemistry showed that PCNA and Rb were expressed in the spontaneous breast cancer tissues, while Ki-67 and P53 were not. The cells of spontaneous breast cancer were arrested in the GI phase of the cell cycle. Conclusion： Maternal inheritance may play an important role in the tumorigenesis of spontaneous breast cancer in TA Ⅱ mice. The frequency of pregnancy may be positively correlated with tumorigenesis. Similar to pregnancy-associated breast cancer in human beings, there was a close relationship between pregnancy and spontaneous breast cancer in mice. High levels of estrogen and progesterone in the blood, the involution of the mammary glands, the changes in immune status during pregnancy and breastfeeding may play a part in tumorigenesis. This research provides a favourable model to study pregnancy-associated breast cancer.