大豆异黄酮在不同的雌激素环境下对MMTV-erbB-2转基因小鼠的作用

Objective To investigate the effect of the soybean isoflavones at different estrogen environments on the pathogenesis of breast cancer in MMTV-erbB-2 transgenic mice. Methods 150 fiveweek-old MMTV-erbB-2 transgenic female mice were phosen and divided into five groups; control group,low estrogen group 1, low estrogen group 2, high estrogen group 1 and high estrogen group 2. The incidence and latent period of breast cancer were observed, and the expression of estrogen receptor (ER) ,progesterone receptor (PR), and proliferating cell nuclear antigen (PCNA) proteins was detected by using immunohistochemistry SP method. Results The incidence of breast cancer in control group, low estrogen group 1, low estrogen group 2, high estrogen group 1 and high estrogen group 2 was 73. 3% , 96. 7% ,30. 3% , 40. 0% and 83. 3% , respectively, with the difference being not significant between control group and high estrogen group 2, and between low estrogen group 1 and high estrogen group 2 (P ＞ 0. 05 ) , but with the difference being significant among the other groups (P ＜ 0. 05 ). There was significant difference in the average latent period of breast cancer among all groups (P ＞ 0. 05 ). There was significant difference in the number of TEB between low-estrogen group 1 and other groups (P ＜ 0.05). There was significant difference in the erbB-2 expression among the groups ( P ＞ 0. 05 ). There was no significant difference in the expression of breast ER and PR between control group and other groups ( P ＞ 0. 05 ). The PCNA expression in breast tumor tissue in low-estrogen group 1 was significantly higher than other groups (P ＜0. 05) , and there was significant difference in the PCNA expression between control group and high estrogen group 2, between low estrogen group 1 and high estrogen group 2 (P ＜ 0. 05). Conclusion The soybean isoflavones at different estrogen environments play different roles in the occurrence and development of MMTV-erbb-2 transgenic mouse mammary tumor. In the context of low estrogen, soybean isoflavones could even promote breast cancer formation and development. In the context of high estrogen, soybean isoflavones could inhibit breast cancer and development.     

大豆异黄酮在不同的雌激素环境下对MMTV-erbB-2转基因小鼠的作用

目的 观察大豆异黄酮在不同的雌激素环境下,对MMTV-erbB-2转基因小鼠的乳腺肿瘤发生及发展的影响.方法 选取鼠龄5周的健康MMTV-erbB-2转基因雌性小鼠150只,分为对照组、低雌激素组1、低雌激素组2、高雌激素组1和高雌激素组2五组,观察各组小鼠乳腺癌的发病率和潜伏期,并采用免疫组织化学染色SP法检测各组小鼠乳腺组织中雌激素受体(ER)、孕激素受体(PR)、增殖细胞核抗原(PCNA)的表达.结果 对照组、低雌激素组1、低雌激素组2、高雌激素组1和高雌激素组2的乳腺癌发病率分别为73.3%、96.7%、30.3%、40.0%和83.3%,对照组与高雌激素组2、低雌激素组1与高雌激素组2发病率比较差异无统计学意义(P＞0.05),其他各组间比较差异有统计学意义(P＜0.05).各组小鼠乳腺癌平均潜伏期比较差异无统计学意义(P＞0.05).低雌激素组1的TEB数量与其他各组比较差异有统计学意义(P＜0.05).erbB-2表达在各组之间表达差异无统计学意义(P＞0.05).低雌激素组1、低雌激素组2、高雌激素组1和高雌激素组2与对照组乳腺ER和PR的表达比较差异无统计学意义(P＞0.05).低雌激素组1实验小鼠发生肿瘤的乳腺组织内PCNA的表达明显高于其他各组(P＜0.05).对照组与高雌激素组2,低雌激素组1与高雌激素组2比较差异有统计学意义(P＜0.05),其他各组间比较差异有统计学意义(P＜0.05).结论 大豆异黄酮在不同的雌激素环境下,对MMTV-erbB-2转基因小鼠乳腺肿瘤的发生及发展起不同的作用.低雌激素环境下大豆异黄酮可促进乳腺肿瘤的发生及发展,高雌激素环境下大豆异黄酮可抑制乳腺肿瘤的发生及发展.

Abstract：

Objective To investigate the effect of the soybean isoflavones at different estrogen environments on the pathogenesis of breast cancer in MMTV-erbB-2 transgenic mice. Methods 150 fiveweek-old MMTV-erbB-2 transgenic female mice were phosen and divided into five groups; control group,low estrogen group 1, low estrogen group 2, high estrogen group 1 and high estrogen group 2. The incidence and latent period of breast cancer were observed, and the expression of estrogen receptor (ER) ,progesterone receptor (PR), and proliferating cell nuclear antigen (PCNA) proteins was detected by using immunohistochemistry SP method. Results The incidence of breast cancer in control group, low estrogen group 1, low estrogen group 2, high estrogen group 1 and high estrogen group 2 was 73. 3% , 96. 7% ,30. 3% , 40. 0% and 83. 3% , respectively, with the difference being not significant between control group and high estrogen group 2, and between low estrogen group 1 and high estrogen group 2 (P ＞ 0. 05 ) , but with the difference being significant among the other groups (P ＜ 0. 05 ). There was significant difference in the average latent period of breast cancer among all groups (P ＞ 0. 05 ). There was significant difference in the number of TEB between low-estrogen group 1 and other groups (P ＜ 0.05). There was significant difference in the erbB-2 expression among the groups ( P ＞ 0. 05 ). There was no significant difference in the expression of breast ER and PR between control group and other groups ( P ＞ 0. 05 ). The PCNA expression in breast tumor tissue in low-estrogen group 1 was significantly higher than other groups (P ＜0. 05) , and there was significant difference in the PCNA expression between control group and high estrogen group 2, between low estrogen group 1 and high estrogen group 2 (P ＜ 0. 05). Conclusion The soybean isoflavones at different estrogen environments play different roles in the occurrence and development of MMTV-erbb-2 transgenic mouse mammary tumor. In the context of low estrogen, soybean isoflavones could even promote breast cancer formation and development. In the context of high estrogen, soybean isoflavones could inhibit breast cancer and development.     

青春期乳房肥大症乳腺组织中芳香化酶P450 mRNA的表达

Objective To investigate the expression status of the P450arom mRNA in breast tissue of pubertal mammary hypertrophy and then explore the possible etiology of pubertal mammary hypertrophy. Methods 15 patients were selected for pubertal mammary hypertrophy group. Breast hypertrophy tissue specimens were collected from the gland excised during reduction mammaplasty. 15 patients with pathologically simple fibroadenoma were used as another control group. Patient approval of participation in this study was obtained preoperatively. The expression of P450arom mRNA was detected by RT-PCR in all the cases above. Results There was no significant difference between the pubertal mammary hypertrophy groups and normal groups on the expression rates of P450arom mRNA. But among the positive cases, the expression of P450arom mRNA within breast tissue were 0.202±0.048 in pubertal mammary hypertrophy group; and 0.159±0.068 in normal group. There was significant difference between the pubertal mammary hypertrophy and normal groups (P < 0.05). Conclusion The expression of P450arom mBNA in pubertal mammary hypertrophy are significantly higher than in normal mammary glandular tissue. The pubertal mammary hypertrophy may be related to the expression status of P450arom mRNA within breast tissue.     

The expression of β-adrenoceptors in human pancreatic cancer cell lines and their roles in cell invasiveness

Objective To investigate the effect and mechanism of β-adrenoceptors on norepi-nephrine-induced invasiveness of pancreatic cancer cell lines. Methods The expression of β-adrenocep-tors mRNA in human pancreatic cancer cell lines MiaPaCa-2 and BxPC3 was detected by using RT-PCR. The cells were randomly divided into control group.10 mol/L NE intervention group, 1 mol/L propranolol intervention group and NE + propranolol intervention group. After 48 h , transwell invasiveness test was used to examine the changes in invasive ability of MiaPaCa-2. The expression of MMP-2, MMP-9 and VEGF mRNA was measured by semi-quantitative RT-PCR. The levels of MMP-2 , MMP-9 and VECF proteins were assayed by immunocytochemistry. Results Both MiaPaCa-2 and BxPC3 expressed β1-and β2-adrenocep-tors. The absorbance ( A) values of invasive cells in NE, NE + propranolol, propranolol and control groups were 0.78±0.02 ,0.32±0.03 ,0.26±0.01 and 0.28±0.02 , respectively, and those in NE intervention group were significantly higher than in control and NE + propranolol groups ( P <0.05) . There was no sig-nificant difference in the number of invasive cells between propranolol and control groups ( P > 0. 05) . In NE group , the expression index of MMP-2 , MMP-9 and VEGF mRNA was 0. 87±0.02 , 1.04±0.02 and 0. 92±0. 01 , and the gray value of the protein expression was 131.20±2.34,105.32±7.21 and 115.60 ±5. 03 , respectively, which were higher than those in control and NE + propranolol groups ( P<0.05). There was no significant difference in the expression levels of MMP-2 , MMP-9 and VEGF mRNA and pro-tein between propranolol and control groups ( P>0.05 ) . Conclusion β-adrenoceptors play an important role in the process of norepinephrine-induced invasiveness of pancreatic cancer cells. NE can promote the invasiveness of MiaPaCa-2 through up-regulating the expression of MMP-2 , MMP-9 and VEGF via β-adre-noceptors.     

The expression of β-adrenoceptors in human pancreatic cancer cell lines and their roles in cell invasiveness

Objective To investigate the effect and mechanism of β-adrenoceptors on norepi-nephrine-induced invasiveness of pancreatic cancer cell lines. Methods The expression of β-adrenocep-tors mRNA in human pancreatic cancer cell lines MiaPaCa-2 and BxPC3 was detected by using RT-PCR. The cells were randomly divided into control group.10 mol/L NE intervention group, 1 mol/L propranolol intervention group and NE + propranolol intervention group. After 48 h , transwell invasiveness test was used to examine the changes in invasive ability of MiaPaCa-2. The expression of MMP-2, MMP-9 and VEGF mRNA was measured by semi-quantitative RT-PCR. The levels of MMP-2 , MMP-9 and VECF proteins were assayed by immunocytochemistry. Results Both MiaPaCa-2 and BxPC3 expressed β1-and β2-adrenocep-tors. The absorbance ( A) values of invasive cells in NE, NE + propranolol, propranolol and control groups were 0.78±0.02 ,0.32±0.03 ,0.26±0.01 and 0.28±0.02 , respectively, and those in NE intervention group were significantly higher than in control and NE + propranolol groups ( P <0.05) . There was no sig-nificant difference in the number of invasive cells between propranolol and control groups ( P > 0. 05) . In NE group , the expression index of MMP-2 , MMP-9 and VEGF mRNA was 0. 87±0.02 , 1.04±0.02 and 0. 92±0. 01 , and the gray value of the protein expression was 131.20±2.34,105.32±7.21 and 115.60 ±5. 03 , respectively, which were higher than those in control and NE + propranolol groups ( P<0.05). There was no significant difference in the expression levels of MMP-2 , MMP-9 and VEGF mRNA and pro-tein between propranolol and control groups ( P>0.05 ) . Conclusion β-adrenoceptors play an important role in the process of norepinephrine-induced invasiveness of pancreatic cancer cells. NE can promote the invasiveness of MiaPaCa-2 through up-regulating the expression of MMP-2 , MMP-9 and VEGF via β-adre-noceptors.     

The expression of β-adrenoceptors in human pancreatic cancer cell lines and their roles in cell invasiveness

Objective To investigate the effect and mechanism of β-adrenoceptors on norepi-nephrine-induced invasiveness of pancreatic cancer cell lines. Methods The expression of β-adrenocep-tors mRNA in human pancreatic cancer cell lines MiaPaCa-2 and BxPC3 was detected by using RT-PCR. The cells were randomly divided into control group.10 mol/L NE intervention group, 1 mol/L propranolol intervention group and NE + propranolol intervention group. After 48 h , transwell invasiveness test was used to examine the changes in invasive ability of MiaPaCa-2. The expression of MMP-2, MMP-9 and VEGF mRNA was measured by semi-quantitative RT-PCR. The levels of MMP-2 , MMP-9 and VECF proteins were assayed by immunocytochemistry. Results Both MiaPaCa-2 and BxPC3 expressed β1-and β2-adrenocep-tors. The absorbance ( A) values of invasive cells in NE, NE + propranolol, propranolol and control groups were 0.78±0.02 ,0.32±0.03 ,0.26±0.01 and 0.28±0.02 , respectively, and those in NE intervention group were significantly higher than in control and NE + propranolol groups ( P <0.05) . There was no sig-nificant difference in the number of invasive cells between propranolol and control groups ( P > 0. 05) . In NE group , the expression index of MMP-2 , MMP-9 and VEGF mRNA was 0. 87±0.02 , 1.04±0.02 and 0. 92±0. 01 , and the gray value of the protein expression was 131.20±2.34,105.32±7.21 and 115.60 ±5. 03 , respectively, which were higher than those in control and NE + propranolol groups ( P<0.05). There was no significant difference in the expression levels of MMP-2 , MMP-9 and VEGF mRNA and pro-tein between propranolol and control groups ( P>0.05 ) . Conclusion β-adrenoceptors play an important role in the process of norepinephrine-induced invasiveness of pancreatic cancer cells. NE can promote the invasiveness of MiaPaCa-2 through up-regulating the expression of MMP-2 , MMP-9 and VEGF via β-adre-noceptors.     

The expression of β-adrenoceptors in human pancreatic cancer cell lines and their roles in cell invasiveness

Objective To investigate the effect and mechanism of β-adrenoceptors on norepi-nephrine-induced invasiveness of pancreatic cancer cell lines. Methods The expression of β-adrenocep-tors mRNA in human pancreatic cancer cell lines MiaPaCa-2 and BxPC3 was detected by using RT-PCR. The cells were randomly divided into control group.10 mol/L NE intervention group, 1 mol/L propranolol intervention group and NE + propranolol intervention group. After 48 h , transwell invasiveness test was used to examine the changes in invasive ability of MiaPaCa-2. The expression of MMP-2, MMP-9 and VEGF mRNA was measured by semi-quantitative RT-PCR. The levels of MMP-2 , MMP-9 and VECF proteins were assayed by immunocytochemistry. Results Both MiaPaCa-2 and BxPC3 expressed β1-and β2-adrenocep-tors. The absorbance ( A) values of invasive cells in NE, NE + propranolol, propranolol and control groups were 0.78±0.02 ,0.32±0.03 ,0.26±0.01 and 0.28±0.02 , respectively, and those in NE intervention group were significantly higher than in control and NE + propranolol groups ( P <0.05) . There was no sig-nificant difference in the number of invasive cells between propranolol and control groups ( P > 0. 05) . In NE group , the expression index of MMP-2 , MMP-9 and VEGF mRNA was 0. 87±0.02 , 1.04±0.02 and 0. 92±0. 01 , and the gray value of the protein expression was 131.20±2.34,105.32±7.21 and 115.60 ±5. 03 , respectively, which were higher than those in control and NE + propranolol groups ( P<0.05). There was no significant difference in the expression levels of MMP-2 , MMP-9 and VEGF mRNA and pro-tein between propranolol and control groups ( P>0.05 ) . Conclusion β-adrenoceptors play an important role in the process of norepinephrine-induced invasiveness of pancreatic cancer cells. NE can promote the invasiveness of MiaPaCa-2 through up-regulating the expression of MMP-2 , MMP-9 and VEGF via β-adre-noceptors.     

The expression of β-adrenoceptors in human pancreatic cancer cell lines and their roles in cell invasiveness

Objective To investigate the effect and mechanism of β-adrenoceptors on norepi-nephrine-induced invasiveness of pancreatic cancer cell lines. Methods The expression of β-adrenocep-tors mRNA in human pancreatic cancer cell lines MiaPaCa-2 and BxPC3 was detected by using RT-PCR. The cells were randomly divided into control group.10 mol/L NE intervention group, 1 mol/L propranolol intervention group and NE + propranolol intervention group. After 48 h , transwell invasiveness test was used to examine the changes in invasive ability of MiaPaCa-2. The expression of MMP-2, MMP-9 and VEGF mRNA was measured by semi-quantitative RT-PCR. The levels of MMP-2 , MMP-9 and VECF proteins were assayed by immunocytochemistry. Results Both MiaPaCa-2 and BxPC3 expressed β1-and β2-adrenocep-tors. The absorbance ( A) values of invasive cells in NE, NE + propranolol, propranolol and control groups were 0.78±0.02 ,0.32±0.03 ,0.26±0.01 and 0.28±0.02 , respectively, and those in NE intervention group were significantly higher than in control and NE + propranolol groups ( P <0.05) . There was no sig-nificant difference in the number of invasive cells between propranolol and control groups ( P > 0. 05) . In NE group , the expression index of MMP-2 , MMP-9 and VEGF mRNA was 0. 87±0.02 , 1.04±0.02 and 0. 92±0. 01 , and the gray value of the protein expression was 131.20±2.34,105.32±7.21 and 115.60 ±5. 03 , respectively, which were higher than those in control and NE + propranolol groups ( P<0.05). There was no significant difference in the expression levels of MMP-2 , MMP-9 and VEGF mRNA and pro-tein between propranolol and control groups ( P>0.05 ) . Conclusion β-adrenoceptors play an important role in the process of norepinephrine-induced invasiveness of pancreatic cancer cells. NE can promote the invasiveness of MiaPaCa-2 through up-regulating the expression of MMP-2 , MMP-9 and VEGF via β-adre-noceptors.     

The expression of β-adrenoceptors in human pancreatic cancer cell lines and their roles in cell invasiveness

Objective To investigate the effect and mechanism of β-adrenoceptors on norepi-nephrine-induced invasiveness of pancreatic cancer cell lines. Methods The expression of β-adrenocep-tors mRNA in human pancreatic cancer cell lines MiaPaCa-2 and BxPC3 was detected by using RT-PCR. The cells were randomly divided into control group.10 mol/L NE intervention group, 1 mol/L propranolol intervention group and NE + propranolol intervention group. After 48 h , transwell invasiveness test was used to examine the changes in invasive ability of MiaPaCa-2. The expression of MMP-2, MMP-9 and VEGF mRNA was measured by semi-quantitative RT-PCR. The levels of MMP-2 , MMP-9 and VECF proteins were assayed by immunocytochemistry. Results Both MiaPaCa-2 and BxPC3 expressed β1-and β2-adrenocep-tors. The absorbance ( A) values of invasive cells in NE, NE + propranolol, propranolol and control groups were 0.78±0.02 ,0.32±0.03 ,0.26±0.01 and 0.28±0.02 , respectively, and those in NE intervention group were significantly higher than in control and NE + propranolol groups ( P <0.05) . There was no sig-nificant difference in the number of invasive cells between propranolol and control groups ( P > 0. 05) . In NE group , the expression index of MMP-2 , MMP-9 and VEGF mRNA was 0. 87±0.02 , 1.04±0.02 and 0. 92±0. 01 , and the gray value of the protein expression was 131.20±2.34,105.32±7.21 and 115.60 ±5. 03 , respectively, which were higher than those in control and NE + propranolol groups ( P<0.05). There was no significant difference in the expression levels of MMP-2 , MMP-9 and VEGF mRNA and pro-tein between propranolol and control groups ( P>0.05 ) . Conclusion β-adrenoceptors play an important role in the process of norepinephrine-induced invasiveness of pancreatic cancer cells. NE can promote the invasiveness of MiaPaCa-2 through up-regulating the expression of MMP-2 , MMP-9 and VEGF via β-adre-noceptors.     

The expression of β-adrenoceptors in human pancreatic cancer cell lines and their roles in cell invasiveness

Objective To investigate the effect and mechanism of β-adrenoceptors on norepi-nephrine-induced invasiveness of pancreatic cancer cell lines. Methods The expression of β-adrenocep-tors mRNA in human pancreatic cancer cell lines MiaPaCa-2 and BxPC3 was detected by using RT-PCR. The cells were randomly divided into control group.10 mol/L NE intervention group, 1 mol/L propranolol intervention group and NE + propranolol intervention group. After 48 h , transwell invasiveness test was used to examine the changes in invasive ability of MiaPaCa-2. The expression of MMP-2, MMP-9 and VEGF mRNA was measured by semi-quantitative RT-PCR. The levels of MMP-2 , MMP-9 and VECF proteins were assayed by immunocytochemistry. Results Both MiaPaCa-2 and BxPC3 expressed β1-and β2-adrenocep-tors. The absorbance ( A) values of invasive cells in NE, NE + propranolol, propranolol and control groups were 0.78±0.02 ,0.32±0.03 ,0.26±0.01 and 0.28±0.02 , respectively, and those in NE intervention group were significantly higher than in control and NE + propranolol groups ( P <0.05) . There was no sig-nificant difference in the number of invasive cells between propranolol and control groups ( P > 0. 05) . In NE group , the expression index of MMP-2 , MMP-9 and VEGF mRNA was 0. 87±0.02 , 1.04±0.02 and 0. 92±0. 01 , and the gray value of the protein expression was 131.20±2.34,105.32±7.21 and 115.60 ±5. 03 , respectively, which were higher than those in control and NE + propranolol groups ( P<0.05). There was no significant difference in the expression levels of MMP-2 , MMP-9 and VEGF mRNA and pro-tein between propranolol and control groups ( P>0.05 ) . Conclusion β-adrenoceptors play an important role in the process of norepinephrine-induced invasiveness of pancreatic cancer cells. NE can promote the invasiveness of MiaPaCa-2 through up-regulating the expression of MMP-2 , MMP-9 and VEGF via β-adre-noceptors.