破骨细胞生成抑制因子在雌激素受体阳性乳腺癌中的生物学作用
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摘要
目的:探讨破骨细胞生成抑制因子(osteoprotegerin,OPG)蛋白在人乳腺癌中的生物学作用。方法:利用Kaplan-Meier plotter数据库分析OPG在人乳腺癌病例中的表达对于病人预后生存的影响。MCF-7去激素培养后,加入17β-雌二醇刺激24 h后,提取总RNA,检测OPG在细胞内的表达情况。利用STRING数据库检索OPG相互作用蛋白。结果:OPG低表达明显减低雌激素受体阳性乳腺癌病人的预后生存时间,而雌激素受体阴性的乳腺癌病人的生存时间不受OPG表达的影响。在17β-雌二醇的刺激下,OPG基因表达水平明显减低。多个因子能够与OPG发生相互作用。结论:OPG可能参与雌激素受体阳性的乳腺癌的转化。
Objective: To evaluate the biological role of osteoprotegerin( OPG) in human breast cancer cells.Methods: We used the Kaplan-Meier plotter database,which the tool enabled the visualization of survival data via Kaplan-Meier graphs,showing the cumulative effect of target gene on survival outcome. Then,Human breast cancer cell line MCF-7 was extracted total RNA after 17β-Estradiol( E2) stimulation for 24 h. The OPG interaction proteins were screened by the string database. Results: A lower expression of OPG was associated with a remarkably shorter survival time in Kaplan-Meier analysis in the estrogen receptor( ER) positive breast cancer( P = 3. 7 E-08),while not in the ER negative breast cancer group( P = 0. 058). E2 reduced the expression of OPG mRNA in breast cancer cell line MCF-7. Conclusion: Our results suggest that OPG contributes to tumor malignant in estrogen receptor positive breast cancer.
Objective: To evaluate the biological role of osteoprotegerin( OPG) in human breast cancer cells.Methods: We used the Kaplan-Meier plotter database,which the tool enabled the visualization of survival data via Kaplan-Meier graphs,showing the cumulative effect of target gene on survival outcome. Then,Human breast cancer cell line MCF-7 was extracted total RNA after 17β-Estradiol( E2) stimulation for 24 h. The OPG interaction proteins were screened by the string database. Results: A lower expression of OPG was associated with a remarkably shorter survival time in Kaplan-Meier analysis in the estrogen receptor( ER) positive breast cancer( P = 3. 7 E-08),while not in the ER negative breast cancer group( P = 0. 058). E2 reduced the expression of OPG mRNA in breast cancer cell line MCF-7. Conclusion: Our results suggest that OPG contributes to tumor malignant in estrogen receptor positive breast cancer.
引文
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[13]Makarovic S,Makarovic Z,Bilic-curcic I,et al.Serum osteoprotegerin in patients with calcified aortic valve stenosis in relation to heart failure[J].Acta Clinica Croatica,2017,56(4):733-741.
[2]Fisher JL,Thomas-Mudge RJ,Elliott J,et al.Osteoprotegerin overexpression by breast cancer cells enhances orthotopic and osseous tumor growth and contrasts with that delivered therapeutically[J].Cancer Research,2006,66(7):3620-3628.
[3]D'oronzo S,Brown J,Coleman R.The role of biomarkers in the management of bone-homing malignancies[J].Journal of Bone Oncology,2017,9:1-9.
[4]Owen S,Sanders AJ,Mason MD,et al.Importance of osteoprotegrin and receptor activator of nuclear factor kappaB in breast cancer response to hepatocyte growth factor and the bone microenvironment in vitro[J].International Journal of Oncology,2016,48(3):919-928.
[5]Chung ST,Geerts D,Roseman K,et al.Osteoprotegerin mediates tumor-promoting effects of interleukin-1beta in breast cancer cells[J].Molecular Cancer,2017,16(1):27.
[6]Ney JT,Juhasz-boess I,Gruenhage F,et al.Genetic polymorphism of the OPG gene associated with breast cancer[J].BMC Cancer,2013,13:40.
[7]Kiesel L,Kohl A.Role of the RANK/RANKL pathway in breast cancer[J].Maturitas,2016,86:10-16.
[8]Park HR,Min SK,Cho HD,et al.Expression of osteoprotegerin and RANK ligand in breast cancer bone metastasis[J].Journal of Korean Medical Science,2003,18(4):541-546.
[9]Onyia JE,Galvin RJ,Ma YL,et al.Novel and selective small molpecule stimulators of osteoprotegerin expression inhibit bone resorption[J].The Journal of Pharmacology and Experimental Therapeutics,2004,309(1):369-379.
[10]Moran O,Zaman T,Eisen A,et al.Serum osteoprotegerin levels and mammographic density among high-risk women[J].Cancer Causes Control,2018,29(6):507-517.
[11]Boudot C,Henaut L,Thiem U,et al.Overexpression of a functional calcium-sensing receptor dramatically increases osteolytic potential of MDA-MB-231 cells in a mouse model of bone metastasis through epiregulin-mediated osteoprotegerin downregulation[J].Oncotarget,2017,8(34):56460-56472.
[12]Goswami S,Sharma-Walia N.Osteoprotegerin rich tumor microenvironment:Implications in breast cancer[J].Oncotarget,2016,7(27):42777-42791.
[13]Makarovic S,Makarovic Z,Bilic-curcic I,et al.Serum osteoprotegerin in patients with calcified aortic valve stenosis in relation to heart failure[J].Acta Clinica Croatica,2017,56(4):733-741.