The Effect Of Estrogen And Progesterone In The Spontaneous Breast Cancer Of TA2 Mice And The Related Mechanisms

Object: To observe the tumorigenesis of spontaneous breast cancer in F1 hybirds of TA1 and TA2, and analyze the relationship of pontaneous breast cancer with congenital causes and acquired predisposition, and to investigate the diversify of the expression of estrogen receptor and progesterone receptor, and to study the effects of exogenous hormones to estrogen receptor and progesterone receptor expression, proliferation and apoptosis. And to investgate the cause and mechanisms involved in it.Methods:1. The hybrids of female TA2 and male TA1 were named F1, the hybrids of female TA1 and male TAII were named F1', then the female and male hybrids of F1 and F1' mate respectively. Tumor morphology was observed under light microscope.2. The expressions of estrogen receptor and progesterone receptor were detected during different periods of pregnancy and lactating by immunohistochemistry and real-time PCR.3.' Exogenous hormones were administrated to ovariectomized mice to mimcry the environment of pregnancy and the expression of estrogen receptor, progesterone receptor, Ki-67 and bcl-2 are detected.Results:1. There are 8 spontaneous breast cancer mice in 9 female F1, average tumor occurred time was 201 days,the average parity was 7.67, there are 8 spontaneous breast cancer mice in 9 female F1, average tumor occurred time was 201 days, the average parity was 7.67. The average tumor occurred time in F1 is shorter than F1' and TA2 spontaneous breast cancer. The tumor was confirmed to be breast cancer by histopathological examination.2. There are stage-variations of estrogen receptor a and progesterone receptor during different periods of pregnancy and lactating. The pregnant mice express higher estrogen receptor a and progesterone receptor than non-pregnancy mice which is consistent with the level of estrogen and progesterone in serum.3. Ovariectomized mice which were administrated estrogen , progesterone, estrogen and progesterone associated have a high expression of estrogen receptor and progesterone receptor. And that have an compact relationship with the level of estrogen. Ovariectomized mice which were administrated estrogen , progesterone , estrogen and progesterone associated have a high expression of ki-67 and bcl-2.Conclusions:1. Congenital causes and acquired predisposition may all play important role in thetumorigenesis of TA2 spontaneous breast cancer. The high incidence of spontaneous breast cancer in TA2 mice may have a relationship with the high level of estrogen and progesterone and their receptors during pregnancy.2. Estrogen and progesterone can promote the proliferation of breast epithelium .During the period of pregnancy, there are high levels of estrogen and progesterone and their receptors. The regularities of the levels of hormone and their receptors' expression are uniform. Hormones binds to the receptors which can promotes the proliferation of epithelium, and promotes the tumorigenesis finally.3. Exogenous hormone can make the mice to a condition of "anembryonic pregnancy". Estrogen can up-regulate the expression of PR. The expression of PR depend on the appearance estrogen and ERα. After estrogen up-regulating PR, at the same time PR binds to progesterone, they can promotes the proliferation and reduce apoptosis of epithelium.