Premium
TREATMENT OF EARLY AND INTERMEDIATE STAGES OF COLORECTAL CANCER WITH EGF‐RECEPTOR RELATED PROTEIN (ERRP).
Author(s) -
Schmelz Eva M,
Xu Hu,
Du Jianhua,
Sarkar Fazlul H,
Rishi Arun,
Majumdar Adhip P
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a31
Subject(s) - colorectal cancer , apoptosis , receptor , cancer research , medicine , chemistry , cancer , endocrinology , biochemistry
Selective anticancer therapies suppress the activation of individual members of the EGFR family. Since most solid tumors express several members of EGFRs, this may not be sufficient to suppress tumor formation. EGF‐Receptor Related Protein (ERRP), a pan‐erbB inhibitor, targets multiple members of EGFRs. In the present study, we studied the effect of recombinant ERRP on the regression of carcinogen‐induced ACF in CF1 mice, representing early stages of colon cancer. As a model for intermediate stages, we used C57Bl/6JMin/+ (Min) mice that carry mutations in the APC gene. ERRP treatment began only after establishment of ACF in CF1 mice or adenoma formation in Min mice. Mice were injected daily with 50 ug ERRP or vehicle (controls) for 10 days. This led to a 40–50% reduction of ACF (p<0.05) and their size (P<0.05). In Min mice, we found a drastic reduction of tumor number and size. The changes in both models were associated with a significant inhibition (50–60%) of proliferation and stimulation (60–70%) of apoptosis in the intestinal mucosa, accompanied by a marked reduction in activation and expression of EGFR, HER‐2 and HER‐3 as well as activation of IGF‐1R and inhibition of NF‐kappa‐B. In contrast, the activity of intestinal alkaline phosphatase, a marker of differentiation, was greatly elevated following ERRP treatment. Taken together, the results indicate that ERRP is effective in inducing regression of existing early and intermediate stages of colorectal cancer. This could partly be attributed to inhibition of EGFRs signaling and induction of differentiation of intestinal mucosa. We suggest that ERRP could be an effective agent for colorectal cancer.