The Expression Of FGF-1 In Breast And Its Effect On Genesis Of Spontaneous Breast Cancer In TA2 Mice

Object:Collect TA2 mice' sera and breast tissues in different phase from the first pregnancy to the forth,observe the diversity of E2 and P in these sera,review the expression of FGF-1 in these breast tissues,approach the dependability of the concentration of E2 and P in sera with the expression of FGF-1 in breast tissues,and than reveal the effect of the frequency of pregnancy on genesis of spontaneous breast cancer in TA2 mice;research the effect of E2 and P on the expression of FGF-1 in breast tissues,through administer exogenous E2 and P to ovariectomized(OVX) mice; compare the difference of the expression of FGF-1 and FGFR1 in normal breast,precancerous breast and breast cancer tissues,approach the role of FGF-1 and FGFR1 in genesis of spontaneous breast cancer in TA2 mice.Methods1.Collect the breast tissues of TA2 mice in pregnancy 5 day(d),10d,15d,20d,after parturition 7d,14d,21d,42d,determine the regular pattern of the expression of FGF-1 in these difference phase breast tissues using real-timePCR and imrnunohistochemistry respectively;and then refer the result of the concentration of E2 and P in sera of these mice,reveal the dependability of the concentration of E2 and P in sera with the expression of FGF-1 in breast tissues.2.Make the OVX mouse model using 20 TA2 mice,divided to 4 groups:E2 group,P group,E2+P group and control group,and then exogenous E2 and P were administrated to ovariectomized mice to mimicry the environment of pregnancy, compare the expression of FGF-1 in these 4 groups after 60 days.3.Collect the sera and breast tissues of the different number of pregnancy of TA2 mice in pregnancy 20d and after parturition 42d;and then determine the contents of E2 and P using electrochemiluminescence,review the breast morphous through HE and coccinellin staining,and detect the expression of FGF-1 and cycinDl.4.Collect breast tissue and breast cancer tissue of normal TA2 female mice of 12 cases and TA2 female mice spontaneous breast cancer of 17 cases,and determine the expression of FGF-1,FGFR1,cyclinDl using immunohistochemistry and real time-PCR. Results:1.E2 and P have similar diversity tendency during different periods of pregnancy and after parturition:before pregnancy 15d,the concentration of E2 and P increase constantly;and then begin decrease,the concentration are lowest in the end lactation.The expression of FGF-1 in these different phase breast tissues has the similar change tendency,except pregnancy 5d.2.E2 and P all can induce the expression of FGF-1 in breast,and E2 has a bigger contribution for the expression of FGF-1 than P.E2+P group has a higher level expression of FGF-1 than other groups(P＜0.05).3.In pregnancy 20d TA2 mice,following the increase of the frequence of pregnancy, breast epithelial cells have proliferation,and the construction of gland alveolus is disorder;the concentration of E2 is increased significantly,but P has a fluctuation up and down;the expression of FGF-1 and cyclinDl is also increased.4.In parturition 42d mice,there was incomplete involution in the third pregnancy. Following the increase of the pregnancy,the concentration of E2 and P increased, but the difference had no statistical significance;meanwhile,the concentration of E2 and P in the first pregnancy were similar to 8-month old mice.And there were the higher expression of FGF-1 and cyclinDl in the third breast involution, compared to the first involution and 8-month old mice(P＜0.05 ).5.The expression of FGF-1,FGFR1 and cyclinDl in breast cancer and precancerous lesions are all higher than in the normal breast(P＜0.05);the expression of cyclinDl is higher in breast cancer tissue than precancerous(P＜0.05);but FGFR1 is lower in breast cancer tissue than precancerous lesions(P＜0.05).Conclusions:1.E2 and P all can induce the expression of FGF-1 in breast,and E2 has a bigger contribution for the expression of FGF-1 than P.In addition,E2 and P have the synergistic effect on the expression of FGF-1 in breast.2.The concentration of E2 and P in sera have a good consistency with the expression of FGF-1 in breast tissues of TA2 mice in different phase of pregnancy and lactation,the environment with the high concentration of E2 and P induce the expression of FGF-1 of breast,and then induce the breast proliferation. 3.The more frequent of pregnancy,the more obvious of breast proliferation in pregnancy,and the more incomplete of breast involution.The increase of number of pregnancy can induce the high expression of cyclinDl maybe through the interaction of the high concentration of E2 and P with FGF-1,the increase of number of pregnancy maybe contribute to the genesis of spontaneous breast cancer in TA2 mice.4.FGF-1 and FGFR1 maybe contribute to the genesis of spontaneous breast cancer in TA2 mice,through regulating the cell cycle and promoting the breast epithelium proliferation.