Department of Pathology, Anhui Medical University, Hefei, Anhui Province, PR China.
Cancer Lett. 2011 Dec 8;311(2):171-6. doi: 10.1016/j.canlet.2011.07.011. Epub 2011 Jul 30.
TA2 mice have a high incidence of spontaneous breast cancer without chemical stimulus. There are two proposed explanations for this phenomenon: one is gravidity and the frequency of pregnancies, and the other is related to the presence of the mouse mammary tumor virus (MMTV). MMTV is hormonally regulated and indirectly promotes tumor formation by leading to the activation of Wnt oncogenes through insertional mutagenesis. In order to clarify the relationship between estrogen, progesterone, MMTV, Wnt oncogenes and breast cancer, ovaries from virgin female TA2 mice were removed and the mice were treated with exogenous estradiol and progesterone in different patterns. This study found that the combination of exogenous estradiol and progesterone induced breast cancer formation in TA2 mice without ovaries. MMTV-LTR mRNA exhibited the highest expression in tumor tissue from the combination treatment group (CT). Mammary tissue from mice in the CT group had the highest Wnt1, Wnt5a, Wnt5b and Wnt10b mRNA expression levels. These results indicate that estradiol and progesterone act in a synergistic manner to upregulate MMTV, which subsequently induces breast cancer in TA2 mice. Various members of the Wnt gene family may play specific roles in different stages of carcinogenesis in TA2 mice.
TA2 小鼠在没有化学刺激的情况下自发发生乳腺癌的发病率很高。对于这种现象有两种解释：一种是怀孕和怀孕次数，另一种与小鼠乳腺肿瘤病毒（MMTV）有关。MMTV 受激素调节，通过插入诱变导致 Wnt 癌基因激活，从而间接促进肿瘤形成。为了阐明雌激素、孕激素、MMTV、Wnt 癌基因与乳腺癌之间的关系，切除了处女雌性 TA2 小鼠的卵巢，并以不同模式用外源性雌二醇和孕激素处理小鼠。本研究发现，在外源性雌二醇和孕激素的联合作用下，无卵巢的 TA2 小鼠会诱发乳腺癌的形成。组合治疗组（CT）的肿瘤组织中 MMTV-LTRmRNA 表达最高。CT 组小鼠的乳腺组织中 Wnt1、Wnt5a、Wnt5b 和 Wnt10bmRNA 表达水平最高。这些结果表明，雌二醇和孕激素以协同方式作用，上调 MMTV，随后在 TA2 小鼠中诱导乳腺癌。Wnt 基因家族的各种成员可能在 TA2 小鼠癌变的不同阶段发挥特定作用。
