Abstract:
:Cyclooxygenase-2 (COX-2) is a transcriptional target and downstream effector of the ErbB-1 (EGFR) and ErbB-2 signaling pathways. We found that anti-EGFR and anti-ErbB-2 antibodies inhibited ERK phosphorylation and downregulated COX-2 protein expression in HCA-7 human colon carcinoma cells. Both antibodies also augmented the cytotoxic effects of the selective COX-2 inhibitor, NS-398. Inhibition of EGFR and ErbB-2 attenuated cell growth by increasing cell death, and the antibody combination suppressed cell growth to a greater extent than did either antibody alone. In conclusion, EGFR and ErbB-2 regulate ERK-mediated COX-2 expression and their selective inhibition enhanced NS-398-induced cell death. Cooperative inhibition of cell growth by EGFR and ErbB-2 blockade suggests the therapeutic potential of targeting multiple ErbB receptors.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Half E,Sun Y,Sinicrope FAdoi
10.1016/j.canlet.2006.11.020subject
Has Abstractpub_date
2007-06-28 00:00:00pages
237-46issue
2eissn
0304-3835issn
1872-7980pii
S0304-3835(06)00656-2journal_volume
251pub_type
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