卵巢癌中AIB1和Bax蛋白表达分析
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摘要
目的检测AIB1蛋白在卵巢癌中的表达情况,及其表达与Bax蛋白表达之间的关系,初步探讨AIB1蛋白在卵巢癌发生发展中的作用。方法应用免疫组化SP法检测20例正常卵巢、22例卵巢良性肿瘤、20例卵巢交界性肿瘤及59例卵巢癌中AIB1、Bax蛋白的表达情况,分析AIB1蛋白表达与卵巢癌临床病理特征的关系,及其表达与Bax蛋白的表达间的关系。结果 AIB1蛋白在正常卵巢、卵巢良性肿瘤、卵巢交界性肿瘤、卵巢癌中阳性表达率分别为10. 00%、22. 73%、35. 00%和59. 32%。卵巢癌AIB1蛋白阳性率显著高于卵巢良性肿瘤和正常卵巢(χ2分别为8. 58和14. 59,P <0. 01)。不同临床分期、组织学分级、ER、PR表达间AIB1蛋白存在明显差异(χ2分别为11. 64、7. 79、8. 87和6. 52,P均小于0. 05)。AIB1与Bax蛋白的表达间存在正相关性(r=0. 34,P <0. 01)。结论卵巢癌中,AIB1蛋白的表达明显升高,且与Bax蛋白的表达呈正相关,与卵巢癌的恶性生物学行为关系密切。AIB1蛋白表达可能通过非激素依赖途径影响了凋亡调节基因如Bax的表达,从而参与了卵巢癌的发生发展。
Objective It was designed to detect the expression of AIB1 protein in ovarian cancer and its relationship with the expression of Bax protein,and to preliminarily explore the role of AIB1 protein in the occurrence and development of ovarian cancer. Methods Immunohistochemical SP method was used to detect the expression of AIB1 and Bax protein in 20 normal ovaries,22 ovarian benign tumors,20 ovarian borderline tumors and 59 ovarian cancers.The relationship between AIB1 protein expression and clinicopathological features of ovarian cancer and its relationship with the expression of Bax protein were analyzed. Results AIB1 protein in normal ovary,ovarian benign tumor,borderline ovarian tumors and ovarian carcinoma and the positive rate was10. 00%,22. 73%,35. 00%,59. 32%.The positive rate of AIB1 protein in ovarian cancer was significantly higher than that of benign ovarian tumors and normal ovaries( the CHI Square was 8. 58 and 14. 59 respectively,the P value was less than 0. 01). There were significant differences in AIB1 protein in different clinical stage,histological grade,ER and PR expression( the CHI Square was 11. 64,7. 79,8. 87 and 6. 52 respectively,all the P value were less than 0. 05). There was a positive correlation between the expression of AIB1 and Bax protein( r = 0. 34,P < 0. 01). Conclusion The expression of AIB1 protein was significantly increased in epithelial ovarian cancer,and was positively correlated with the expression of Bax protein,which was closely related to the malignant biological behavior of epithelial ovarian cancer. The expression of AIB1 protein may affect the expression of apoptosis regulating genes,such as Bax,through hormone-independent pathway,thus participating in the development of ovarian cancer.
Objective It was designed to detect the expression of AIB1 protein in ovarian cancer and its relationship with the expression of Bax protein,and to preliminarily explore the role of AIB1 protein in the occurrence and development of ovarian cancer. Methods Immunohistochemical SP method was used to detect the expression of AIB1 and Bax protein in 20 normal ovaries,22 ovarian benign tumors,20 ovarian borderline tumors and 59 ovarian cancers.The relationship between AIB1 protein expression and clinicopathological features of ovarian cancer and its relationship with the expression of Bax protein were analyzed. Results AIB1 protein in normal ovary,ovarian benign tumor,borderline ovarian tumors and ovarian carcinoma and the positive rate was10. 00%,22. 73%,35. 00%,59. 32%.The positive rate of AIB1 protein in ovarian cancer was significantly higher than that of benign ovarian tumors and normal ovaries( the CHI Square was 8. 58 and 14. 59 respectively,the P value was less than 0. 01). There were significant differences in AIB1 protein in different clinical stage,histological grade,ER and PR expression( the CHI Square was 11. 64,7. 79,8. 87 and 6. 52 respectively,all the P value were less than 0. 05). There was a positive correlation between the expression of AIB1 and Bax protein( r = 0. 34,P < 0. 01). Conclusion The expression of AIB1 protein was significantly increased in epithelial ovarian cancer,and was positively correlated with the expression of Bax protein,which was closely related to the malignant biological behavior of epithelial ovarian cancer. The expression of AIB1 protein may affect the expression of apoptosis regulating genes,such as Bax,through hormone-independent pathway,thus participating in the development of ovarian cancer.
引文
[1]Chen L,Wang C,Zhang X,et al. AIB1 genomic amplification predicts poor clinical outcomes in female glioma patients[J]. J Cancer,2016,7(14):2052-2060.
[2]You D,Zhao H,Wang Y,et al. Acetylation Enhances the Promoting Role of AIB1 in Breast Cancer Cell Proliferation[J]. Mol Cells,2016,39(9):663-668.
[3]Zeng J,Yang J,Chen DB,et al. The Mechanisms by which Bax Induces the Apoptosis of Human Ovarian Cancer Cells[J]. Sichuan Da Xue Xue Bao Yi Xue Ban,2015,46(5):697-701.
[4]Alkner S,Jensen MB,Rasmussen BB,et al. Prognostic and predictive importance of the estrogen receptor coactivator AIB1 in a randomized trial comparing adjuvant letrozole and tamoxifen therapy in postmenopausal breast cancer:the Danish cohort of BIG 1-98[J]. Breast Cancer Res Treat,2017,166(2):481-490.
[5]Manmuan S,Sakunrangsit N,Ketchart W. Salinomycin overcomes acquired tamoxifen resistance through AIB1 and inhibits cancer cell invasion in endocrine resistant breast?cancer[J]. Clin Exp Pharmacol Physiol,2017,44(10):1042-1052.
[6]Li L,Gan ZH,Qin L,et al. AIB1 regulates the ovarian cancer cell cycle through TUG1[J]. Eur Rev Med Pharmacol Sci,2017,21(24):5610-5617.
[7]Han G,Xie S,Fang H,et al. The AIB1 gene polyglutamine repeat length polymorphism contributes to risk of epithelial ovarian cancer risk:a case-control study[J]. Tumour Biol,2015,36(1):371-374.
[8]Peng X,Li F,Wang P,et al. Apelin-13 induces MCF-7cell proliferation and invasion via phosphorylation of ERK1/2[J]. Int J Mol Med,2015,36(3):733-738.
[9]Liu X,Dong J,Cai W,et al. The Effect of Thymoquinone on Apoptosis of SK-OV-3 Ovarian Cancer Cell by Regulation of Bcl-2 and Bax[J]. Int J Gynecol Cancer,2017,27(8):1596-1601.
[10]Xiao S,Chen F,Gao C. Antitumor activity of 4-O-Methylhonokiol in human oral cancer cells is mediated via ROS generation,disruption of mitochondrial potential,cell cycle arrest and modulation of Bcl-2/Bax proteins[J]. J BUON,2017,22(6):1577-1581.
[11]Ghibelli L,Diederich M. Multistep and multitask Bax activation[J]. Mitochondrion,2010,10(6):604-613.
[12]Zhang RT,Shi HR,Ren F,et al. The aberrant upstream pathway regulations of CDK1 protein were implicated in the proliferation and apoptosis of ovarian cancer cells[J]. J Ovarian Res,2017,10:60.
[13]Matsumura S,Ohta T,Yamanouchi K,et al. Activation of estrogen receptorαby estradiol and cisplatin induces platinum-resistance in ovarian cancer cells[J]. Cancer Biol Ther,2017,18(9):730-739.
[14]王颖欣,韩萍,陈燕. Bcl-2蛋白和Bax蛋白在上皮性卵巢癌中的表达及临床意义[J].西部医学,2011,23(5):814-816.
[15]Chang AK,Wu H. The role of AIB1 in breast cancer[J].Oncol Lett,2012,4(4):588-594.
[16]Li R,Chen Y,Shu WX,et al. Involvement of SRC-3 in deguelin-induced apoptosis in Jurkat cells[J]. Int J Hematol,2009,89(5):628-635.
[17]Zhao Z,Zhang X,Wen L,et al. Steroid receptor coactivator-3 is a pivotal target of gambogic acid in B-cell NonHodgkin lymphoma and an inducer of histone H3 deacetylation[J]. Eur J Pharmacol,2016,789:46-59.
[18]Sahin E,Eraslan Sahin M,Dolanbay M,et al. Induction of apoptosis by metformin and progesterone in estrogen-induced endometrial hyperplasia in rats:involvement of the bcl-2family proteins[J]. Gynecol Endocrinol,2017,27:1-4.
[2]You D,Zhao H,Wang Y,et al. Acetylation Enhances the Promoting Role of AIB1 in Breast Cancer Cell Proliferation[J]. Mol Cells,2016,39(9):663-668.
[3]Zeng J,Yang J,Chen DB,et al. The Mechanisms by which Bax Induces the Apoptosis of Human Ovarian Cancer Cells[J]. Sichuan Da Xue Xue Bao Yi Xue Ban,2015,46(5):697-701.
[4]Alkner S,Jensen MB,Rasmussen BB,et al. Prognostic and predictive importance of the estrogen receptor coactivator AIB1 in a randomized trial comparing adjuvant letrozole and tamoxifen therapy in postmenopausal breast cancer:the Danish cohort of BIG 1-98[J]. Breast Cancer Res Treat,2017,166(2):481-490.
[5]Manmuan S,Sakunrangsit N,Ketchart W. Salinomycin overcomes acquired tamoxifen resistance through AIB1 and inhibits cancer cell invasion in endocrine resistant breast?cancer[J]. Clin Exp Pharmacol Physiol,2017,44(10):1042-1052.
[6]Li L,Gan ZH,Qin L,et al. AIB1 regulates the ovarian cancer cell cycle through TUG1[J]. Eur Rev Med Pharmacol Sci,2017,21(24):5610-5617.
[7]Han G,Xie S,Fang H,et al. The AIB1 gene polyglutamine repeat length polymorphism contributes to risk of epithelial ovarian cancer risk:a case-control study[J]. Tumour Biol,2015,36(1):371-374.
[8]Peng X,Li F,Wang P,et al. Apelin-13 induces MCF-7cell proliferation and invasion via phosphorylation of ERK1/2[J]. Int J Mol Med,2015,36(3):733-738.
[9]Liu X,Dong J,Cai W,et al. The Effect of Thymoquinone on Apoptosis of SK-OV-3 Ovarian Cancer Cell by Regulation of Bcl-2 and Bax[J]. Int J Gynecol Cancer,2017,27(8):1596-1601.
[10]Xiao S,Chen F,Gao C. Antitumor activity of 4-O-Methylhonokiol in human oral cancer cells is mediated via ROS generation,disruption of mitochondrial potential,cell cycle arrest and modulation of Bcl-2/Bax proteins[J]. J BUON,2017,22(6):1577-1581.
[11]Ghibelli L,Diederich M. Multistep and multitask Bax activation[J]. Mitochondrion,2010,10(6):604-613.
[12]Zhang RT,Shi HR,Ren F,et al. The aberrant upstream pathway regulations of CDK1 protein were implicated in the proliferation and apoptosis of ovarian cancer cells[J]. J Ovarian Res,2017,10:60.
[13]Matsumura S,Ohta T,Yamanouchi K,et al. Activation of estrogen receptorαby estradiol and cisplatin induces platinum-resistance in ovarian cancer cells[J]. Cancer Biol Ther,2017,18(9):730-739.
[14]王颖欣,韩萍,陈燕. Bcl-2蛋白和Bax蛋白在上皮性卵巢癌中的表达及临床意义[J].西部医学,2011,23(5):814-816.
[15]Chang AK,Wu H. The role of AIB1 in breast cancer[J].Oncol Lett,2012,4(4):588-594.
[16]Li R,Chen Y,Shu WX,et al. Involvement of SRC-3 in deguelin-induced apoptosis in Jurkat cells[J]. Int J Hematol,2009,89(5):628-635.
[17]Zhao Z,Zhang X,Wen L,et al. Steroid receptor coactivator-3 is a pivotal target of gambogic acid in B-cell NonHodgkin lymphoma and an inducer of histone H3 deacetylation[J]. Eur J Pharmacol,2016,789:46-59.
[18]Sahin E,Eraslan Sahin M,Dolanbay M,et al. Induction of apoptosis by metformin and progesterone in estrogen-induced endometrial hyperplasia in rats:involvement of the bcl-2family proteins[J]. Gynecol Endocrinol,2017,27:1-4.