RGD Reference Report - Genomic analysis of alachlor-induced oncogenesis in rat olfactory mucosa. - Rat Genome Database

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Genomic analysis of alachlor-induced oncogenesis in rat olfactory mucosa.

Authors: Genter, MB  Burman, DM  Vijayakumar, S  Ebert, CL  Aronow, BJ 
Citation: Genter MB, etal., Physiol Genomics. 2002 Dec 26;12(1):35-45.
RGD ID: 1599782
Pubmed: PMID:12419858   (View Abstract at PubMed)
DOI: DOI:10.1152/physiolgenomics.00120.2002   (Journal Full-text)

Alachlor induces olfactory mucosal tumors in rats in a highly ordered temporal process. We used GeneChip analysis to test the hypothesis that histological progression and oncogenic transformation are accompanied by gene expression changes that might yield clues as to the molecular pathogenesis of tumor formation. Acute alachlor exposure caused upregulation of matrix metalloproteinases (MMP)-2 and -9, tissue inhibitor of metalloproteinase-1, carboxypeptidase Z, and other genes related to extracellular matrix homeostasis. Heme oxygenase was upregulated acutely and maintained elevated expression. Expression of ebnerin, related to the putative human tumor suppressor gene DMBT1, progressively increased in alachlor-treated olfactory mucosa. Progression from adenomas to adenocarcinoma was correlated with upregulation of genes in the wnt signaling pathway. Activated wnt signaling was confirmed by immunohistochemical localization of beta-catenin to nuclei of adenocarcinomas, but not earlier lesions. These observations suggest that initiation and progression of alachlor-induced olfactory mucosal tumors is associated with alterations in extracellular matrix components, induction of oxidative stress, upregulation of ebnerin, and final transformation to a malignant state by wnt pathway activation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Nose Neoplasms  ISODmbt1 (Rattus norvegicus)1599782; 1599782mRNA and Protein:increased expressionRGD 
Nose Neoplasms  IEP 1599782mRNA and Protein:increased expressionRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to biphenyl  IEP 1599782 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dmbt1  (deleted in malignant brain tumors 1)

Genes (Mus musculus)
Dmbt1  (deleted in malignant brain tumors 1)

Genes (Homo sapiens)
DMBT1  (deleted in malignant brain tumors 1)


Additional Information