Age-related loss of EGF-receptor related protein (ERRP) in the aging colon is a potential risk factor for colon cancer.
Although in Fischer-344 rats, aging is associated with increased activation of EGF-receptor (EGFR) in mucosa of much of the gastrointestinal tract, including the colon, regulation of this process is poorly understood. We hypothesize that loss of suppressor of EGFR may partly be responsible for this process. To test this hypothesis, we examined the expression of EGFR related protein (ERRP), a recently identified negative regulator of EGFR, in the colonic mucosa during aging and following administration of the colonic carcinogen dimethylhydrazine (DMH) that resulted in the formation of aberrant crypt foci (ACF), which are considered to be precursor of adenoma and carcinoma. In Fischer-344 rats, aging is associated with increased activation of EGFR in the colonic mucosa, as evidenced by 30-35% increase in the levels of tyrosine phosphorylated EGFR in the proximal and distal colon of aged (20-22 months old) than in young (4-6 months old) rats. In contrast, the levels of ERRP in both regions of the colon of aged rats were decreased by 50-60%, compared to their younger counterparts. Administration of DMH, which induced a greater number of ACF in the colon of aged rats than in young animals, resulted in a corresponding reduction in ERRP in the colon. These results suggest that loss of ERRP expression is a common event during aging and early stages of chemically induced colon cancer. We also suggest that loss of ERRP could be a risk factor for developing colorectal cancer in the older population.
Schmelz
Eva M
EM
Karmanos Cancer Institute, Wayne State University School of Medicine, VA Medical Center-151, 4646 John R Street, Detroit, MI 48201, USA. schmelze@karmanos.org
Levi
Edi
E
Du
Jianhua
J
Xu
Hu
H
Majumdar
Adhip P N
AP
D019813:1,2-Dimethylhydrazine / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000209:etiology*; D066246:ErbB Receptors / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012307:Risk Factors
D002273:Carcinogens; D006023:Glycoproteins; C483803:Egfr protein, rat; D066246:ErbB Receptors; D019813:1,2-Dimethylhydrazine