Basic-alimentary tractEpidermal growth factor receptor-related protein: a potential therapeutic agent for colorectal cancer☆
Section snippets
Cell lines
Colon cancer cell lines HCT-116 and Caco-2 and monkey kidney COS-7 cells, obtained from the American Type Culture Collection (Rockville, MD), were maintained in Dulbecco’s modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS), penicillin (10,000 U/mL), streptomycin (10,000 U/mL), and amphotericin (25 μL/mL) at 37°C in an atmosphere of 95% air and 5% CO2.
Cell proliferation
This was assessed by 3-(4,5-dimethylthialzol-2yl)-2,5-diphenyltetrazolium bromide assay according to the procedure
Results
The fact that the ORF of ERRP contains a signal peptide composed of 24 amino acids, together with our observation that ERRP is present in the conditioned media derived from drosophila S2 cells (Figure 1), suggests that ERRP is a secretory protein. To further test this possibility that ERRP is a secretary protein, we generated a construct expressing polyhistidine and Myc-tagged ERRP protein. This construct or the vector plasmid (control) was subsequently transfected into COS-7 cells, and the
Discussion
Accumulating evidence suggests that downstream blocking of the EGFR signaling pathway is an effective therapeutic approach for the treatment and prevention of many epithelial malignancies, particularly those whose growth is regulated by the EGF family of peptides. This may be the most relevant area for use of ERRP. There are several strategies under investigation to block binding of growth factor to receptor. Previously, Wagner et al.25showed that transfection into pancreatic cancer cells
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2006, Journal of Biological ChemistryCitation Excerpt :Collectively, our data suggest that retroviral transduction of ERRP results in inhibition of EGFR and induction of apoptosis. These data corroborate our previous observations demonstrating attenuation of EGFR and stimulation of apoptosis of cancer cells by recombinant ERRP (14, 15). Whether apoptosis induction by ERRP involves CARP-1 was investigated by transducing cells with ERRP or by treating cells with purified ERRP for various times.
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Supported by grants to Dr. Majumdar from the Department of Veterans Affairs and the National Institute on Aging (AG 14343).