DOI QR코드

DOI QR Code

Silencing of Lysyl Oxidase Gene Expression by RNA Interference Suppresses Metastasis of Breast Cancer

  • Liu, Jian-Lun (Department of Breast Surgery, Cancer Hospital, Guangxi Medical University) ;
  • Wei, Wei (Department of Breast Surgery, Cancer Hospital, Guangxi Medical University) ;
  • Tang, Wei (Department of Breast Surgery, Cancer Hospital, Guangxi Medical University) ;
  • Jiang, Yi (Department of Breast Surgery, Cancer Hospital, Guangxi Medical University) ;
  • Yang, Hua-Wei (Department of Breast Surgery, Cancer Hospital, Guangxi Medical University) ;
  • Li, Jing-Tao (Department of Breast Surgery, Cancer Hospital, Guangxi Medical University) ;
  • Zhou, Xiao (Department of Breast Surgery, Cancer Hospital, Guangxi Medical University)
  • 발행 : 2012.07.31

초록

Objective: The aim of this study was to investigate possible mechanisms of LOX gene effects on invasion and metastasis of breast cancer cells by RNA interference. Methods: LOX-RNAi-LV was designed, synthesized, and then transfected into a breast cancer cell line (MDA-MB-231). Expression of LOX, MMP-2 and MMP-9 was determined by real-time PCR, and protein expression of LOX by Western blotting. Cell migration and invasiveness were assessed with Transwell chambers. A total of 111 cases of breast cancer tissues, cancer-adjacent normal breast tissues, and 20 cases of benign lesion tissues were assessed by immunohistochemistry. Results: Expression of LOX mRNA and protein was suppressed, and the expression of MMP-2 and MMP-9 was significantly lower in the RNAi group than the control group (P<0.05), after LOX-RNAi-LV was transfection into MDA-MB-231 cells. Migration and invasion abilities were obviously inhibited. The expression of LOX protein in breast cancer, cancer-adjacent normal breast tissues and benign breast tumor were 48.6% (54/111), 26.1% (29/111), 20.0% (4/20), respectively, associations being noted with clinical stage, lymph node metastasis, tumor size and ER, PR, HER2, but not age. LOX protein was positively correlated with MMP-2 and MMP-9. Conclusion: LOX displayed an important role in invasion and metastasis of breast cancer by regulating MMP-2 and MMP-9 expression which probably exerted synergistic effects on the extracellular matrix (ECM).

키워드

참고문헌

  1. Akiri G, Sabo E, Dafni H, et al (2003). Lysyl oxidase-related protein-1 promotes tumorfibrosis and tumor progression in vivo. Cancer Res, 63, 1657-66.
  2. Erler JT, Bennewith KL, Nicolau M, et al (2006). Lysyl oxidase is essential for hypoxia-induced metastasis. Nature, 440, 1222-6. https://doi.org/10.1038/nature04695
  3. Erler JT, Giaccia AJ (2006). Lysyl oxidase mediates hypoxic control of metastasis. Cancer Res, 66, 10238-41. https://doi.org/10.1158/0008-5472.CAN-06-3197
  4. Fong SF, Dietzsch E, Fong KS, et al (2007). Lysyl oxidase-like 2 expression is increased in colon and esophageal tumors and asociated with lass differentiated colon turners. Genes Chromosomes Cancer, 46, 644-55. https://doi.org/10.1002/gcc.20444
  5. Hafez MM, Hassan ZK, Zekri AR, et al (2012). MicroRNAs and metastasis-related gene expression in Egyptian breast cancer patients. Asian Pac J Cancer Prev, 13, 591-8. https://doi.org/10.7314/APJCP.2012.13.2.591
  6. Holtmeier C, Gorogh T, Beier U, et al (2003). Overexpression of a novel lysyl oxidase-like gene in human head and neck squamous cell carcinomas. Anticancer Res, 23, 2585-91.
  7. Jing DC, Blidaru A, Condrea I, et al (2006). MMP-9 and MMP-2 gelatinases and TIMP-1 and TIMP-2 inhibitors in breast cancer: correlations with prognostic factors. J Cell Mol Med, 10, 499-510. https://doi.org/10.1111/j.1582-4934.2006.tb00415.x
  8. Kirschmann DA, Payne SL, Seftor EA , et al (2005). Tumor suppressor gene Maspin and hypoxia inversely regulate lysyl oxidase facilitated breast cancer motility. Proc Amer Assoc Cancer Res, 46, 57-8.
  9. Kirschmann DA, Seftor EA, Fong SF, et al (2002). A molecular role for lysyl oxidase in breast cancer invasion. Cancer Res, 62, 4478-83.
  10. Lhotak S, Elavathil LJ, Vukmirovic-Popovic, et al (2000). Immunolocalization of matrix- metallo-proteinases and their inhibitors in clinical specimens of bone metastasis from breast carcinoma. Clin Exp Metastasis, 18, 463-70. https://doi.org/10.1023/A:1011800919981
  11. Liotta LA, Steeg PA, Stetler-stevenson WG (1991). Canaer metastasis and angiogensis: and imbalance of positive negative regulation. Cell, 64, 327-31. https://doi.org/10.1016/0092-8674(91)90642-C
  12. Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C (T)) Method. Methods, 25, 402-8. https://doi.org/10.1006/meth.2001.1262
  13. Loh SY, Chew SL, Lee SY (2011). Physical Activity and Women with Breast Cancer: Insights from Expert Patients. Asian Pac J Cancer Prev, 12, 87-94.
  14. Nakopoulou L, Katsarou S, Giannopoulou I, et al (2002). Correlation of tissue inhibitor of metalloproteinase- 2 with proliferative actixity and patients sunal in breast cancer. Mod Patho1, 15, 26-34. https://doi.org/10.1038/modpathol.3880486
  15. Payne SL, Angela R. Hess AR, et al (2005). Lysyl oxidase facilitates intracellular signaling in invasive breast cancer cells. Proc Amer Assoc Cancer Res, 46, 67-8.
  16. Peyrol S, Raccurt M, Gerard F, et al (1997). Lysy1 oxidase gene expression in the stromal reaction to in situ and invasive ductal breast carcinoma. Am J Pathol, 150, 497-507.
  17. Sulaiman S, Shahril MR, Shaharudin SH, et al (2011). Fat intake and its relationship with pre- and postmenopausal breast cancer risk: a case-control study in Malaysia. Asian Pac J Cancer Prev, 12, 2167-78.
  18. Talvensaari MA, Paakko P, Turpeenniemi HT (2003). Matrix metalloproteinase-2 (MMP-2) is associated with sunixal in breast carcinoma. Br J Cancer, 89, 1270-5. https://doi.org/10.1038/sj.bjc.6601238
  19. Woznick AR, Braddock AL, Dulai M, et al (2005). Lysyl oxidase expression in bronchogenic carcinoma. Am J surg, 189, 297-301. https://doi.org/10.1016/j.amjsurg.2004.11.031
  20. Yu Q, Stamenkovic I (2000). Cell surface-localized matrixmetalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes, 14, 163-76.
  21. Zucker S, Hymowitz M, Rollo EE, et al (2001). Tumorigenic potential of extracellar matrix metalloproteinase inducer. Am J Pathol, 158, 1921-8. https://doi.org/10.1016/S0002-9440(10)64660-3

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