DOI QR코드

DOI QR Code

Insulin Promotes Proliferation and Migration of Breast Cancer Cells through the Extracellular Regulated Kinase Pathway

  • Pan, Feng (Department of Laboratory Medicine, The Affiliated Hospital of Hangzhou Normal University) ;
  • Hong, Li-Quan (Department of Laboratory Medicine, The Affiliated Hospital of Hangzhou Normal University)
  • Published : 2014.08.15

Abstract

The present study was undertaken to determine the roles of insulin in the growth of transplanted breast cancer in nude mice, and the proliferation and migration of MCF-7 human breast cancer cells and assess its influence on downstream signaling pathways. In a xenograft mouse model with injection of MCF-7 human breast cancer cells, tumor size was measured every other day. The insulin level and insulin receptor (IR) were increased in the breast cancer patient tissues. Insulin injected subcutaneously around the tumor site in mice caused increase in the size and weight of tumor masses, and promoted proliferation and migration of MCF-7 cells. The effects of insulin on the increase in the proliferation and migration of MCF-7 human breast cancer cells were abolished by pretreatment with the extracellular regulated kinase (ERK) inhibitor PD98059. Insulin increased the phosphorylation of ERK in the MCF-7 cells. These results indicate that insulin promotes the growth of breast cancer in nude mice, and increases the proliferation and migration of MCF-7 human breast cancer cells via the ERK pathway.

Keywords

References

  1. Alegre M, Knowles H, Robison A, et al (2013). Mechanics behind breast cancer prevention - focus on obesity, exercise and dietary fat. Asian Pac J Cancer Prev, 14, 2207-12. https://doi.org/10.7314/APJCP.2013.14.4.2207
  2. Belardi V, Gallagher J, Novosyadlyy R, et al (2013). Insulin and IGFs in obesity-related breast cancer. J Mammary Gland Biol Neoplasia, 18, 277-89. https://doi.org/10.1007/s10911-013-9303-7
  3. Cao W, Wang X, Li C (2013). Hereditary breast cancer in the Han Chinese population. J Epidemiol, 23, 75-84.
  4. Demark-Wahnefried W, Campbell L, Hayes C (2012). Weight management and its role in breast cancer rehabilitation. Cancer, 118, 2277-87. https://doi.org/10.1002/cncr.27466
  5. Foti P, Paonessa F, Chiefari E, et al (2009). New target genes for the peroxisome proliferator-activated receptor-gamma (PPARgamma) antitumour activity: Perspectives from the insulin receptor. PPAR Res, 571365.
  6. Gallagher J, Alikhani N, Tobin-Hess A, et al (2013). Insulin receptor phosphorylation by endogenous insulin or the insulin analog AspB10 promotes mammary tumor growth independent of the IGF-I receptor. Diabetes, 62, 3553-60. https://doi.org/10.2337/db13-0249
  7. Gomez-Hernandez A, Escribano O, Perdomo L, et al (2013). Implication of insulin receptor A isoform and IRA/IGF-IR hybrid receptors in the aortic vascular smooth muscle cell proliferation: role of TNF-alpha and IGF-II. Endocrinology, 154, 2352-64. https://doi.org/10.1210/en.2012-2161
  8. Hauner D, Janni W, Rack B, et al (2011). The effect of overweight and nutrition on prognosis in breast cancer. Dtsch Arztebl Int, 108, 795-801.
  9. Irwin L, Alvarez-Reeves M, Cadmus L, et al (2009). Exercise improves body fat, lean mass, and bone mass in breast cancer survivors. Obesity, 17, 1534-41. https://doi.org/10.1038/oby.2009.18
  10. Jemal A, Siegel R, Xu J, et al (2010). Cancer statistics. CA Cancer J Clin, 60, 277-300. https://doi.org/10.3322/caac.20073
  11. Karlstad O, Linde S, Vestergaard P, et al (2013). Use of insulin and insulin analogs and risk of cancer- systematic review and meta-analysis of observational studies. Curr Drug Saf, 8, 333-48. https://doi.org/10.2174/15680266113136660067
  12. Khan S, Shukla S, Sinha S, et al (2013). Role of adipokines and cytokines in obesity-associated breast cancer: Therapeutic targets. Cytokine Growth Factor Rev, 24, 503-13. https://doi.org/10.1016/j.cytogfr.2013.10.001
  13. Kobayashi S, Sugiura H, Ando Y, et al (2012). Reproductive history and breast cancer risk. Breast Cancer, 19, 302-8. https://doi.org/10.1007/s12282-012-0384-8
  14. Kujiraoka T, Satoh Y, AyaoriM, et al (2013). Hepatic extracellular signal-regulated kinase 2 suppresses endoplasmic reticulum stress and protects from oxidative stress and endothelial dysfunction. J Am Heart Assoc, 2, 361. https://doi.org/10.1161/JAHA.113.000361
  15. Maccio A, Madeddu C (2011). Obesity, inflammation, and postmenopausal breast cancer: therapeutic implications. Scientific World Journal, 11, 2020-36. https://doi.org/10.1100/2011/806787
  16. Martin C, Bratton R, Zhu Y, et al (2012). Insulin-like growth factor-1 signaling regulates miRNA expression in MCF-7 breast cancer cell line. PLoS One, 7, 49067. https://doi.org/10.1371/journal.pone.0049067
  17. Minatoya M, Kutomi G, Asakura S, et al (2013). Equol, adiponectin, insulin levels and risk of breast cancer. Asian Pac J Cancer Prev, 14, 2191-9. https://doi.org/10.7314/APJCP.2013.14.4.2191
  18. Pasanisi P, Bruno E, Manoukian S (2013). A randomized controlled trial of diet and physical activity in BRCA mutation carriers. Fam Cancer, 13, 181-7
  19. Salisbury B, Morris Z, Tomblin K, et al (2013). Aryl hydrocarbon receptor ligands inhibit igf-ii and adipokine stimulated breast cancer cell proliferation. ISRN Endocrinol, 104850.
  20. Sangrajrang S, Chaiwerawattana A, Ploysawang P, et al (2013). Obesity, diet and physical inactivity and risk of breast cancer in Thai women. Asian Pac J Cancer Prev, 14, 7023-7. https://doi.org/10.7314/APJCP.2013.14.11.7023
  21. Savry A, Carre M, Berges R, et al (2013). Bcl-2-enhanced efficacy of microtubule-targeting chemotherapy through Bim overexpression: implications for cancer treatment. Review of. Neoplasia, 15, 49-60. https://doi.org/10.1593/neo.121074
  22. Schmitz H, Ahmed L, Hannan J, et al (2005). Safety and efficacy of weight training in recent breast cancer survivors to alter body composition, insulin, and insulin-like growth factor axis proteins. Cancer Epidemiol Biomarkers Prev, 14, 1672-80. https://doi.org/10.1158/1055-9965.EPI-04-0736
  23. Woody S, Stall R, Ramos J, et al (2013). Regulation of myosin light chain kinase during insulin-stimulated glucose uptake in 3T3-L1 adipocytes. PLoS One, 8, 77248. https://doi.org/10.1371/journal.pone.0077248
  24. Xia Y, Guo G, Ji X, et al (2014). The G801A polymorphism in the CXCL12 gene and risk of breast carcinoma: evidence from a meta-analysis including 2, 931 subjects. Asian Pac J Cancer Prev, 15, 2857-61. https://doi.org/10.7314/APJCP.2014.15.6.2857
  25. Yamaguchi Y, Seino Y, Takei H, (2013). Detection of estrogenindependent growth-stimulating activity in breast cancer tissues: implication for tumor aggressiveness. Cancer Microenviron.
  26. Yang Y, Yee D. (2012). Targeting insulin and insulin-like growth factor signaling in breast cancer. J Mammary Gland Biol Neoplasia, 17, 251-61. https://doi.org/10.1007/s10911-012-9268-y
  27. Yaw H, Shariff M, Kandiah M, et al (2014). Diet and physical activity in relation to weight change among breast cancer patients. Asian Pac J Cancer Prev, 15, 39-44. https://doi.org/10.7314/APJCP.2014.15.1.39
  28. Yu H, Zhang M, Zhao Y (2013). Insulin promotes proliferation of skeletal myoblast cells through PI3K/Akt and MEK/ERK pathways in rats. Sheng Li Xue Bao, 65, 19-25.
  29. Yu W, Gu JC, Liu JZ, et al (2010). Regulation of estrogen receptors alpha and beta in human breast carcinoma by exogenous leptin in nude mouse xenograft model. Chin Med J, 123, 337-43.

Cited by

  1. A Novel All-trans Retinoid Acid Derivative N-(3-trifluoromethyl-phenyl)-Retinamide Inhibits Lung Adenocarcinoma A549 Cell Migration through Down-regulating Expression of Myosin Light Chain Kinase vol.15, pp.18, 2014, https://doi.org/10.7314/APJCP.2014.15.18.7687
  2. Detection of PIK3CA Gene Mutations with HRM Analysis and Association with IGFBP-5 Expression Levels in Breast Cancer vol.15, pp.21, 2014, https://doi.org/10.7314/APJCP.2014.15.21.9327
  3. ERK1/2 promoted proliferation and inhibited apoptosis of human cervical cancer cells and regulated the expression of c-Fos and c-Jun proteins vol.32, pp.3, 2015, https://doi.org/10.1007/s12032-015-0490-5
  4. Role of EHD2 in migration and invasion of human breast cancer cells vol.36, pp.5, 2015, https://doi.org/10.1007/s13277-014-3011-9
  5. Insulin Receptor Isoforms in Physiology and Disease: An Updated View vol.38, pp.5, 2017, https://doi.org/10.1210/er.2017-00073
  6. Mesenchymal stem cell-conditioned medium promotes MDA-MB-231 cell migration and inhibits A549 cell migration by regulating insulin receptor and human epidermal growth factor receptor 3 phosphorylation vol.13, pp.3, 2017, https://doi.org/10.3892/ol.2017.5641
  7. Ixodid tick salivary gland extracts suppress human transforming growth factor-β1 triggered signalling pathways in cervical carcinoma cells vol.73, pp.11, 2018, https://doi.org/10.2478/s11756-018-0129-z
  8. Effect of insulin on thyroid cell proliferation, tumor cell migration, and potentially related mechanisms pp.1532-4206, 2018, https://doi.org/10.1080/07435800.2018.1522641
  9. Sub-lethal Doses of Polybrominated Diphenyl Ethers, in Vitro, Promote Oxidative Stress and Modulate Molecular Markers Related to Cell Cycle, Antioxidant Balance and Cellular Energy Management vol.16, pp.4, 2019, https://doi.org/10.3390/ijerph16040588