Examining the expression of low-density lipoprotein receptor (LDLR) and low-density lipoprotein receptor-related protein 6 (LRP6) genes in breast cancer cell lines

Document Type : Original article

Authors

1 Behbahan FDepartment of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iranaculty of Medical Sciences, Behbahan, Iran

2 Behbahan Faculty of Medical Sciences, Behbahan, Iran

3 Department of Biochemistry, School of Medicine Hormozgan University of Medical Sciences, Hormozgan, Iran

4 Autophagy Research Center, Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Cholesterol and the Wnt/β-catenin pathway have an effective role in the proliferation, survival, drug resistance, immune exhaustion, and metastasis of all types of cancer cells. Considering the role of LDLR and LRP6 proteins in cholesterol uptake by cells and activation of Wnt/β-catenin pathway, this study aims to examine the gene expression of LDLR and LRP6 in cell lines of breast cancer. Human breast cancer cell lines MCF7, MD468 and SKBR3 were cultured in suitable conditions and after extracting total RNA from them, real-Time PCR was used to measure the levels of gene expression for LDLR and LRP6. Our results showed that the expression of LDLR and LRP6 genes is significantly increased in MCF7 and MD468 cells compared to SKBR3 cells. These results suggest that LRP6 and LDLR can be considered as a therapeutic target in tumors that have a genetic profile similar to MCF7 and MD468 cells

Keywords


  1. Subramaniam DS, Isaacs C. Utilizing prognostic and predictive factors in breast cancer. Curr Treat Options Oncol 2005;6:147-159.
  2. Liu J, Xu A, Lam KS, Wong NS, Chen J, Shepherd PR, Wang Y. Cholesterol-induced mammary tumorigenesis is enhanced by adiponectin deficiency: role of LDL receptor upregulation. Oncotarget 2013;4:1804-1818.
  3. Lee K, Kruper L, Dieli-Conwright CM, Mortimer JE. The impact of obesity on breast cancer diagnosis and treatment. Curr Oncol Rep 2019;21:41.
  4. Li X, Liu Zl, Wu YT, Wu H, Dai W, Arshad B, Xu Z, Wu KN, Kong LQ. Status of lipid and lipoprotein in female breast cancer patients at initial diagnosis and during chemotherapy. Lipids Health Dis 2018;17:91.
  5. Wolfe AR, Atkinson RL, Reddy JP, Debeb BG, Larson R, Li L, Masuda H, Brewer T, Atkinson BJ, Brewster A, Ueno NT, Woodward WA. High-density and very-low-density lipoprotein have opposing roles in regulating tumor-initiating cells and sensitivity to radiation in inflammatory breast cancer. Int J Radiat Oncol Biol Phys 2015;91:1072-1080.
  6. Moon RT. Wnt/β-catenin pathway. Sci STKE 2005;2005:cm1.
  7. Dong Y, Zhang Y, Kang W, Wang G, Chen H, Higashimori A, Nakatsu G, Go M, Tong JHM, Zheng S, To KF, Sung JJY, Yang X, Ng SSm, Yu J. VSTM2A suppresses colorectal cancer and antagonizes Wnt signaling receptor LRP6. Theranostics 2019;9:6517-6531.
  8. Rismani E, Fazeli MS, Mahmoodzadeh H, Movassagh A, Azami S, Karimipoor M, Teimoori-Toolabi L. Pattern of LRP6 gene expression in tumoral tissues of colorectal cancer. Cancer Biomark 2017;19:151-159.
  9. Lacroix M, Leclercq G. Relevance of breast cancer cell lines as models for breast tumours: an update. Breast Cancer Res Treat 2004;83:249-289.
  10. Vargo-Gogola T, Rosen JM. Modelling breast cancer: one size does not fit all. Nat Rev Cancer 2007;7:659-672.
  11. Kao J, Salari K, Bocanegra M, Choi YL, Girard L, Gandhi J, Kwei KA, Hernandez-Boussard T, Wang P, Gazdar AF, Minna JD, Pollack JR. Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery. PLoS One 2009;4:e6146.
  12. Thulasiraman P, McAndrews DJ, Mohiudddin IQ. Curcumin restores sensitivity to retinoic acid in triple negative breast cancer cells. BMC Cancer 2014;14:724
  13. Pires L, Hegg R, Freitas FR, Tavares ER, Almeida CP, Baracat EC, Maranhao RC. Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer. Braz J Med Biol Res 2012;45:557-564.
  14. Rodrigues dos Santos C, Domingues G, Matias I, Matos J, Fonseca I, de Almeida JM, Dias S. LDL-cholesterol signaling induces breast cancer proliferation and invasion. Lipids Health Dis 2014;13:16.
  15. Torres CG, Ramírez ME, Cruz P, Epuñan MJ, Valladares LE, Sierralta WD. 27-hydroxycholesterol induces the transition of MCF7 cells into a mesenchymal phenotype. Oncol Rep 2011;26:389-397.
  16. Cruz P, Torres C, Ramírez ME, Epuñán MJ, Valladares LE, Sierralta WD. Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol. Exp Ther Med 2010; 1:531-536.
  17. Yang L, Wu X, Wang Y, Zhang K, Wu J, Yuan YC, Deng X, Chen L, Kim CCH, Lau S, Somlo G, Yen Y. FZD7 has a critical role in cell proliferation in triple negative breast cancer. Oncogene 2011;30:4437-4446.
  18. DiMeo TA, Anderson K, Phadke P, Feng C, Perou CM, Naber S, Naber S, Kuperwasser C. A novel lung metastasis signature links Wnt signaling with cancer cell self-renewal and epithelial-mesenchymal transition in basal-like breast cancer. Cancer Res 2009; 69:5364-5373.