Document Detail


Expression analysis of the group IIA secretory phospholipase A(2) in mice with differential susceptibility to azoxymethane-induced colon tumorigenesis.
MedLine Citation:
PMID:  10657948     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The murine non-pancreatic secretory phospholipase A(2) (sPLA(2)) has been proposed as a tumor modifier of multiple intestinal neoplasia (Min). A genetic polymorphism in the mouse gene that causes a disruption in exon 3 results in loss of functional protein. Mouse strains with a disrupted sPLA(2) gene are susceptible to the Min phenotype and develop numerous intestinal polyps, whereas mice with normal sPLA(2) develop only a limited number of polyps. The following study was undertaken to test the hypothesis that sPLA(2) plays an equivalent role in murine susceptibility to the colon carcinogen azoxymethane (AOM). sPLA(2) status was confirmed by sequencing in mice that are highly susceptible (A/J), susceptible (SWR/J) and resistant (AKR/J) to AOM-induced tumorigenesis. Constitutive expression of sPLA(2) mRNA was compared in small intestine and colon of untreated mice using semi-quantitative RT-PCR. Whereas mRNA expression was nearly absent in A/J mice, AKR/J mice exhibited extensive expression throughout the intestine. Despite the wild-type sPLA(2) gene, colonic mRNA expression in SWR/J mice was significantly lower relative to AKR/J. Immunohistochemical analysis of sPLA(2) protein confirmed the mRNA data. The effect of AOM on colonic sPLA(2) expression was also examined. Twenty-four weeks after the last of six weekly injections of AOM (10 mg/kg i.p.), RT-PCR analysis of distal colons revealed a significant increase in mRNA in normal-appearing epithelium and tumor tissue from AOM-treated mice relative to controls. However, there was no corresponding increase in protein expression in A/J mice. The absence of sPLA(2) expression within control colons of tumor-susceptible A/J mice together with low expression in SWR/J colons is consistent with its potential role as an intestinal tumor modifier, but the carcinogen-induced increase in expression raises doubts as to the significance of sPLA(2) in inhibiting carcinogenesis.
Authors:
A Papanikolaou; Q S Wang; R Mulherkar; A Bolt; D W Rosenberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Carcinogenesis     Volume:  21     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-04-03     Completed Date:  2000-04-03     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  133-8     Citation Subset:  IM    
Affiliation:
Toxicology Program, Department of Pharmaceutical Sciences, University of Connecticut, 372 Fairfield Road, Storrs, CT 06269-2092, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Azoxymethane / toxicity*
Carcinogens / toxicity*
Colon / enzymology
Colonic Neoplasms / chemically induced,  enzymology,  genetics*
Colonic Polyps / chemically induced,  enzymology,  genetics*
Exons / genetics
Genetic Predisposition to Disease
Group II Phospholipases A2
Intestines / enzymology*
Mice
Mice, Inbred A
Mice, Inbred AKR
Mice, Inbred Strains
Phenotype
Phospholipases A / biosynthesis*,  genetics
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
1T32ES07163/ES/NIEHS NIH HHS; CA81428-01/CA/NCI NIH HHS; DK49805-01/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Carcinogens; 25843-45-2/Azoxymethane; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Group II Phospholipases A2

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