Chinese Medical E-ournals Database

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2013, Vol. 09 ›› Issue (02): 150 -154. doi: 10.3877/cma.j.issn.1673-5250.2013.02.005

Special Issue:

Original Article

Study on the Effect of Abnormal Expression of Annexin A2 Regulated by Ubiquitination in the Pathological Process of Breast Cancer

Tian-yong XING1, Ling-mi HOU2, Shi-shan DENG3()   

  1. 1. Department of General Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
  • Received:2013-01-08 Revised:2013-03-15 Published:2013-04-01
  • Corresponding author: Shi-shan DENG
  • About author:
    (Corresponding author: DENG Shi-shan, Email: )
Objective

To study the abnormal expression of annexin A2 and the ubiquitniation regulatory mechanism in breast cancer tissue, relationship between annexin A2 and TNM clinical stages of breast cancer, effects of abnormal expression of ubiquitination regulation annexin A2 in the process of breast cancer development.

Methods

From September 2008 to September 2009, a total of 10 cases of women were diagnosed as breast cancer. The breast cancer tissue samples by pathology (n=10) and para-tumor relatively normal tissue based on morphology (n=10) (diameter>2 cm) which were surgically removed from those 10 cases patients. Samples of tissues were preserved with liquid nitrogen as soon as it had been excised. Two-D polyacrylamide gel eletrophresis (2-DE) was applied to separate protein of breast cancer tissue and para-tumor normal tissues, and confirmed ubiquitination (immunoproteomics) was detected by Western bolting with PDQuest software (7.1), then MALDI-TOF-TOF, MS-MS and bioinformatics analysis was performed to obtain differential proteins ubiquitinated. Different expression of annexin A2 in breast cancer tissue and para-tumor normal tissues, as well as their relationship with TNM clinical stages of breast cancer were observed and analyzed by applying the method of immunohistochemical staining and SPSS 13.0. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Affiliated Hospital of North Sichuan Medical College. Informed consent was obtained from each participates.

Results

Four proteins with identified by immunoproteomics, they were, SMT3A, PSMA1, annexin A2 and RPS12. By immunohistochemical staining analysis, positive expression rates and strong positive expression rates of annexin A2 in breast cancer of 0, Ⅰ, Ⅱ and Ⅲ TNM clinical stages and the adjacent normal tissues were 75.0%(6/8)/37.5%(3/8), 100.0%(14/14)/42.9%(6/14), 100.0%(10/10)/66.7%(4/6), and 100.0%(6/6)/50.0%(5/10), respectively. There had statistically significant difference between expression positive rate and strong positive rates at different TNM clinical stages in breast cancer (P<0.05). The expression levels of annexin A2 had positive correlation with TNM clinical stages (r=0.508, P<0.05).

Conclusions

Expression of annexin A2 in breast cancer tissues is regulated by ubiquitination, and more later the TNM clinical stages in breast cancer, more higher the expression of annexin A2. Over-expression of annexin A2 regulated by ubiquitination may be involve in breast cancer.

图1 人乳腺癌组织与癌旁正常组织2-DE产生的凝胶进行Western bloting的结果(→:乳腺癌组织标本中明显差异表达的蛋白质点a,b,c,d. No:乳腺癌癌旁正常组织.Ca:乳腺癌组织)(7 cm胶条,蛋白质免疫印迹法)
Figure 1 The Western Bloting test result of gel from breast cancer tissue and para-tumor tissue.(→:Proteins with apparent difference expression a,b, c, d in breast cancer tissue. No: Para-tumor normal tissue. Ca: Breast cancer tissue)(7 cm stripe,Western bloting)
图2 同一样本2-DE产生的另一凝胶进行考马斯亮蓝R-250染色得到对应差异蛋白质点(→:乳腺癌组织标本中明显差异表达的蛋白质点a,b,c,d.No:乳腺癌癌旁正常组织.Ca:乳腺癌组织)(7 cm胶条,考马斯亮蓝R-250染色)
Figure 2 Comparative different proteins of the same sample by staining with CBB-R-250(→:Proteins with apparent difference expression a,b, c, d in breast cancer tissue. No: Para-tumor normal tissue. Ca: Breast cancer tissue)(7 cm stripe,CBB-R-250)
表1 明显差异表达的蛋白质的基质辅助激光解吸/电离时间飞行时间质谱、质谱/质谱串联
Table 1 Results by MALDI-TOF-MS and MS-MS of high expression protein in breast cancer tissues
表2 annexin A2的表达与乳腺癌TNM临床分期的关系[n(%)]
Table 2 Relationship between the expression of annexin A2 and TNM clinical stage of breast cancer[n(%)]
[1]
Nandi D, Tahiliani P, Kumtrr A, et al.The ubiquitin-proteasome system[J].J Biosci, 2006, 31(1):137-155.
[2]
Fan M, Bigsby RM, Nephew KP.The NEDD8 pathway is required for proteasome-mediated degradation of human estrogen receptor (ER)-alpha and essential for the antiproliferative activity of ICI 182 780 in ERalpha-positive breast cancer cells[J].Mol Endocrinol, 2003, 17(3):356-365.
[3]
Kundranda MN, Ray S, Saria M, et al.Annexins expressed on the cell surface serve as receptors for adhesion to immobilized fetuin-A[J].Biochim Biophys Acta, 2004, 1693(2):111-123.
[4]
Hayes MJ, Shao D, Baily M, et al.Regulation of actin dynamics by annexin 2[J].EMBO J, 2006, 25(9):1816-1826.
[5]
Semov A, Moreno MJ, Onichtchenko A, et al.Metastasis-associated protein S100A4 induces angiogenesis through interaction with Annexin Ⅱ and accelerated plasmin formation[J].Biol Chem, 2005, 280(21):20833-20841.
[6]
Semov A, Moreno MJ, Onichtchenko A, et al.Metastasis-associated protein S100A4 induces angiogenesis through interaction with annexin Ⅱ and accelerated plasmin formation[J]. Biol Chem, 2005, 280(21):20833.
[7]
Frohlich M, Motte P, Galvin K, et al.Enhanced expres-sion of the protin kinase substrate p36 in human hepatocelhar carcinoma[J].Mol Cell Biol, 1990, 10:3216.
[8]
Sharma MR, Koltowski L, Ownbey RT, et al.Angiogenesis-associated protein annexin Ⅱ in breast cancer:Selective expression in invasive breast cancer and contribution to tumor invasion and progression[J].Exp Mol Pathol, 2006, 8l(2):146-156.
[9]
Yan GR, Ding W, Xu SH, et al.Characterization of phosphoproteins in gastric cancer secretome[J].OMICS, 2011, 15(1-2):83-90.
[10]
Andronicos NM, Ranson M.The topology of plasminogen binding and activation on the surface of human breast cancer cell[J].Br J Cancer, 2001, 85(6):909-916.
[11]
Zhang J, Guo B, Zhang Y, et al.Silencing of the annexin Ⅱ gene down-regulates the levels of S100A10, c-Myc, and plasmin and inhibits breast cancer cell proliferation and invasion[J].Saudi Med, 2010, 31(4):374-381.
[12]
Sharma M, Ownbey RT, Sharma MC, et al.Breast cancer cell surface annexin Ⅱ induces cell migration and neoangiogenesis via t-PA dependent plasmin generation[J].Exp Mol Pathol, 2010, 88(2):278-286.
[13]
Xing TY, Hou LM, Wang JG, et al. The difference expression of annexin a2 in breast carcinoma and the significance[J]. Chin J Clinicians:Ed, 2011, 5 (18):5310-5313.
[14]
Hou LM, Xing TY, Deng SS. Progress of the study of relations between annexin a2 and breast cancer[J].Chin J Clinicians:Ed, 2011, 5 (14):4206-4208.
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