Insulin-like growth factor receptor I signaling in a breast cancer cell line
Keywords:
breast neoplasms, cell line, receptor, IGF type 1, mitogen-activated protein kinase 1, 1-phosphatidylinositol 3-kinase, oncogene protein v-akt
Abstract
Introduction. In vitro studies strongly suggest that proliferation, migration and cell survival of breast cancer cell lines are significantly affected by activation of the IGF type 1 receptor (IGF-IR).Objective. The phosphorylation by IGF-I of IGF-IR and the intracellular signaling molecules Akt (PI-3K pathway) and Erk1/2 (MAPK pathway) was characterized in a human breast cancer cell lines.
Materials and methods. The study compared a standard breast adenocarcinoma line (MCF-7) cell line with a line (CSC 1595) derived from an infiltrating ductal breast cancer in a Colombian patient. The CSC 1595 and MCF-7 cell lines were cultured in DMEM supplemented with 10% fetal bovine serum, 2 mM glutamine, 100 U/ml penicillin, and 100 μg/ml streptomycin and grown at 37°C in 5% CO2 atmosphere and 95% humidity. Cell extracts were prepared, followed by immunoprecipitation and immunoblotting with specific anti-pIGF-IR, anti-pERK1/2 and anti-pAkt antibodies.
Results. After 5 minute stimulation with IGF-I, 70% of the IGF-IR was phosphorylated in the cell line CSC 1595 and 25% in MCF-7. In addition, Akt (oncogene protein v-akt) and ERK1/2 (extracellular signal-regulated MAP kinases) were phosphorylated. Basal and stimulated levels of phosphorylated ERK1/2 were substantially higher compared to those in the MCF-7 cell line.
Conclusions. The IGF-IR and MAPK kinase pathway involving proteins ERK1/2 showed more significant phosphorylation in the 1,595 cells compared to the observed in the MCF-7 cell line. Since the IGF-IR is the major activator of this pathway it may play an important role in ductal infiltrating breast cancer tumor growth and metastases.
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References
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27. Piñeros M, Ferlay J, Murillo R. Cancer incidence estimates at the national and district levels in Colombia. Salud Pública Mex. 2006;48:455-65.
28. Baserga R. Customizing the targeting of IGF-1 receptor. Future Oncol. 2009;5:43-50.
2. Riley L, Desai D. The molecular basis of cancer and the development of targeted therapy. Surg Clin North Am. 2009;89:1-15.
3. Hurvitz S, Pietras R. Rational management of endocrine resistance in breast cancer: A comprehensive review of estrogen receptor, treatment options and future directions. Cancer. 2008;113:2385-97.
4. Milanezi F, Carvalho S, Schmitt FC. EGFR/HER2 in breast cancer: a biological approach for molecular diagnosis and therapy. Expert Rev Mol Diagn. 2008;8:417-34.
5. Nicoletto MO, Donach M, Nicolo AD, Artioli G, Banna G, Monfardini S. BRCA-1 and BRCA-2 mutations as prognostic factors in clinical practice and genetic counselling. Cancer Treat Rev. 2001;27:295-304.
6. Hirohashi S, Kanai Y. Cell adhesion system and human cancer morphogenesis. Cancer Sci. 2003;94:575-81.
7. Troussard AA, McDonald PC, Wederell ED, Mawji NM, Filipenko NR, Gelmon KA, et al. Preferential dependence of breast cancer cells versus normal cells on integrin-linked kinase for protein kinase B/Akt activation and cell survival. Cancer Res. 2006;66:393-403.
8. Pezzino V, Papa V, Milazzo G, Gliozzo B, Russo P, Scalia P. Insulin-like growth factor-I (IGF-I) receptors in breast cancer. Ann NY Acad Sci. 1996;784:189-201.
9. Gee JM, Robertson JF, Gutteridge E, Ellis IO, Pinder SE, Rubini M, et al. Epidermal growth factor receptor/HER2/insulin-like growth factor receptor signalling and oestrogen receptor activity in clinical breast cancer. Endocr Relat. 2005;12:S99-111.
10. Massarweh S, Osborne CK, Creighton CJ, Qin L, Tsimelzon A, Huang S, et al. Tamoxifen resistance in breast tumors is driven by growth factor receptor signaling with repression of classic estrogen receptor genomic function. Cancer Res. 2008;68:826-33.
11. Schiff R, Massarweh SA, Shou J, Bharwani L, Mohsin SK, Osborne CK. Cross-talk between estrogen receptor and growth factor pathways as a molecular target for overcoming endocrine resistance. Clin Cancer Res. 2004;10:331s-6s.
12. Nicholson RI, Hutcheson IR, Knowlden JM, Jones HE, Harper ME, Jordan N, et al. Nonendocrine pathways and endocrine resistance. Clin Cancer Res. 2004;10:346s-54s.
13. Lann D, LeRoith D. The role of endocrine insulin-like growth factor-I and insulin in breast cancer. J Mammary Gland Biol Neoplasia. 2008;13:371-9.
14. Yu H, Rohan T. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst. 2000;92:1472-89.
15. LeRoith D, Roberts CT. The insulin-like growth factor system and cancer. Cancer Lett. 2003;195:127-37.
16. Yanochko G, Eckhart W. Type I insulin-like growth factor receptor over-expression induces proliferation and anti-apoptotic signaling in a three-dimensional culture model of breast epithelial cells. Breast Cancer Res. 2006;8:R18.
17. Sun H, Tu X, Baserga R. Dual regulation of upstream binding factor 1 levels by IRS-1 and ERKs in IGF-1-receptor signaling. J Cell Physiol. 2007;212:780-6.
18. Castro C, Riveros T, Jiménez G, Téllez N. Inducción de apoptosis por el principio activo citotóxico de Espeletia killipii Cuatr. sobre líneas celulares humanas. Rev Bras Farmacogn. 2007;17:497-500.
19. Castro C, Riveros T. Registro del Laboratorio de Biología Experimental. Bogotá, D. C.: Instituto Nacional de Cancerología E. S. E.; 1999.
20. Dickson RB, Bates SE, McManaway ME, Lippman ME. Characterization of estrogen responsive transforming activity in human breast cancer cell lines. Cancer Res. 1986;46:1707-13.
21. Frasca F, Pandini G, Sciacca L, Pezzino V, Squatrito S, Belfiore A, et al. The role of insulin receptors and IGF-I receptors in cancer and other diseases. Arch Physiol Biochem. 2008;114:23-37.
22. Sarfstein R, Maor S, Reizner N, Abramovitch S, Werner H. Transcriptional regulation of the insulin-like growth factor-I receptor gene in breast cancer. Mol Cell Endocrinol. 2006;252:241-6.
23. Dillon RL, White DE, Muller WJ. The phosphatidyl inositol 3-kinase signaling network: implications for human breast cancer. Oncogene. 2007;26:1338-45.
24. Whyte J, Bergin O, Bianchi A, McNally S, Martin F. Key signalling nodes in mammary gland development and cancer. Mitogen-activated protein kinase signalling in experimental models of breast cancer progression and in mammary gland development. Breast Cancer Res. 2009;11:209.
25. Lannigan DA. Estrogen receptor phosphorylation. Steroids. 2003;68:1-9.
26. Gee JM, Howell A, Gullick WJ, Benz CC, Sutherland RL, Santen RJ, et al. Consensus statement. Workshop on therapeutic resistance in breast cancer: impact of growth factor signalling pathways and implications for future treatment. Endocr Relat Cancer. 2005;12:S1-7.
27. Piñeros M, Ferlay J, Murillo R. Cancer incidence estimates at the national and district levels in Colombia. Salud Pública Mex. 2006;48:455-65.
28. Baserga R. Customizing the targeting of IGF-1 receptor. Future Oncol. 2009;5:43-50.
How to Cite
1.
Mejía W, Castro C, Umaña A, de Castro C, Riveros T, Sánchez-Gómez M. Insulin-like growth factor receptor I signaling in a breast cancer cell line. biomedica [Internet]. 2010 Dec. 1 [cited 2024 May 19];30(4):551-8. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/293
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Published
2010-12-01
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