Document Detail


EGFR regulation of colon cancer stem-like cells during aging and in response to the colonic carcinogen dimethylhydrazine.
MedLine Citation:
PMID:  22281474     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
One of the most consistent pathological conditions in the gastrointestinal tract with advancing age is malignancy, particularly gastrointestinal cancers, the incidence of which increases sharply with aging. Although the reasons for the age-related rise in colorectal cancer are not fully understood, we hypothesize that aging increases susceptibility of the colon to carcinogen(s)/toxicant(s), leading to an increase in cancer stem-like cells (CSLCs) that express cancer stem cell markers, in the colonic mucosa. The current study demonstrates that aging is associated with increased expression of several colon CSLC markers [CD44, CD166, and aldehyde dehydrogenase 1 (ALDH-1)] and a higher proportion of cells expressing these markers. Aging is also accompanied by increased expression of miR-21 in colon. These increases are further increased in response to the colonic carcinogen dimethylhydrazine (DMH). Aging is also associated with increased tyrosine-phosphorylated epidermal growth factor receptor (EGFR). Inhibition of EGFR using the EGFR inhibitor cetuximab abrogated the age-related increase in CD166 and ALDH-1 as well as miRNA (miR)-21. Our results provide new evidence that aging and DMH are associated with increases in CSLC biomarkers and miR21, each of which have been linked to colorectal cancer. EGFR inhibition attenuates these changes, indicating a role for EGFR in age- and mutagen-associated changes in CSLCs.
Authors:
Jyoti Nautiyal; Jianhua Du; Yingjie Yu; Shailender S Kanwar; Edi Levi; Adhip P N Majumdar
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-01-26
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  302     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-02     Completed Date:  2012-05-30     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G655-63     Citation Subset:  IM    
Affiliation:
Veterans Affairs Medical Center, Detroit, Michigan 48201, USA.
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MeSH Terms
Descriptor/Qualifier:
Aging / pathology,  physiology*
Animals
Antibodies, Monoclonal / pharmacology
Antineoplastic Agents / pharmacology
Carcinogens / toxicity*
Colon / cytology,  metabolism
Colonic Neoplasms / metabolism,  pathology
Dimethylhydrazines / toxicity*
Gene Expression Regulation, Neoplastic / drug effects,  physiology
Intestinal Mucosa / cytology
Male
MicroRNAs / genetics,  metabolism
Neoplastic Stem Cells / drug effects*,  metabolism*
Rats
Receptor, Epidermal Growth Factor / genetics,  metabolism*
Tumor Markers, Biological / metabolism
Grant Support
ID/Acronym/Agency:
AG-014343/AG/NIA NIH HHS; AG-014343-12S1/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antineoplastic Agents; 0/Carcinogens; 0/Dimethylhydrazines; 0/Egfr protein, rat; 0/MicroRNAs; 0/Tumor Markers, Biological; EC 2.7.10.1/Receptor, Epidermal Growth Factor; PQX0D8J21J/cetuximab
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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