RGD Reference Report - alpha(2)-Macroglobulin: a novel cytochemical marker characterizing preneoplastic and neoplastic rat liver lesions negative for hitherto established cytochemical markers. - Rat Genome Database

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alpha(2)-Macroglobulin: a novel cytochemical marker characterizing preneoplastic and neoplastic rat liver lesions negative for hitherto established cytochemical markers.

Authors: Sukata, T  Uwagawa, S  Ozaki, K  Sumida, K  Kikuchi, K  Kushida, M  Saito, K  Morimura, K  Oeda, K  Okuno, Y  Mikami, N  Fukushima, S 
Citation: Sukata T, etal., Am J Pathol 2004 Nov;165(5):1479-88.
RGD ID: 1358261
Pubmed: PMID:15509519   (View Abstract at PubMed)
PMCID: PMC1618685   (View Article at PubMed Central)

We tried to identify a novel marker characteristic for rat hepatocellular preneoplastic and neoplastic lesions, undetectable by well established cytochemical markers. Glutathione S-transferase placental (GST-P)-negative hepatocellular altered foci (HAF), hepatocellular adenoma (HCA), and hepatocellular carcinoma (HCC) were generated by two initiation-promotion models with N-nitrosodiethylamine (NDEN) and peroxisome proliferators, Wy-14,643 and clofibrate. Total RNAs isolated from laser-microdissected GST-P-negative HAF (amphophilic cell foci) and adjacent normal tissues were applied to microarray analysis. As a result, five up-regulated genes were identified, and further detailed examinations of the gene demonstrating most fluctuation, ie, that for alpha(2)-macroglobulin (alpha(2)M) were performed. In reverse transcriptase-polymerase chain reaction, alpha(2)M mRNA was overexpressed not only in amphophilic GST-P-negative HAF but also in amphophilic GST-P-negative HCA and HCC. In situ hybridization showed accumulation of alpha(2)M mRNA to be evenly distributed within GST-P-negative HAF (predominantly amphophilic cell foci). Distinctive immunohistochemical staining for alpha(2)M could be consistently demonstrated in GST-P-negative HAF, HCA, and HCC induced not only by peroxisome proliferators but also N-nitrosodiethylamine alone. Thus our findings suggest that alpha(2)M is an important novel cytochemical marker to identify hepatocellular preneoplastic and neoplastic lesions, particularly amphophilic cell foci, undetectable by established cytochemical markers and is tightly linked to rat hepatocarcinogenesis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hepatocellular adenoma  ISOA2m (Rattus norvegicus)1358261; 1358261mRNA and protein:increased expression:liver:RGD 
hepatocellular adenoma  IEP 1358261mRNA and protein:increased expression:liver:RGD 
hepatocellular carcinoma  ISOA2m (Rattus norvegicus)1358261; 1358261mRNA and protein:increased expression:liver:RGD 
hepatocellular carcinoma  IEP 1358261mRNA and protein:increased expression:liver:RGD 

Objects Annotated

Genes (Rattus norvegicus)
A2m  (alpha-2-macroglobulin)

Genes (Mus musculus)
A2m  (alpha-2-macroglobulin)

Genes (Homo sapiens)
A2M  (alpha-2-macroglobulin)


Additional Information