Mejía Wilson, Castro Carlos, Umaña Adriana, de Castro Clemencia, Riveros Tulia, Sánchez-Gómez Myriam
Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C, Colombia.
Biomedica. 2010 Oct-Dec;30(4):551-8.
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).
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.
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.
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.
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.
