RGD Reference Report - Overexpression of members of the AP-1 transcriptional factor family from an early stage of renal carcinogenesis and inhibition of cell growth by AP-1 gene antisense oligonucleotides in the Tsc2 gene mutant (Eker) rat model. - Rat Genome Database

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Overexpression of members of the AP-1 transcriptional factor family from an early stage of renal carcinogenesis and inhibition of cell growth by AP-1 gene antisense oligonucleotides in the Tsc2 gene mutant (Eker) rat model.

Authors: Urakami, S  Tsuchiya, H  Orimoto, K  Kobayashi, T  Igawa, M  Hino, O 
Citation: Urakami S, etal., Biochem Biophys Res Commun. 1997 Dec 8;241(1):24-30.
RGD ID: 2293758
Pubmed: PMID:9405228   (View Abstract at PubMed)
DOI: DOI:10.1006/bbrc.1997.7731   (Journal Full-text)

We previously isolated subtracted cDNA clones for genes having increased expression in Tsc2 gene mutant (Eker) rat renal carcinomas (RCs). Among them, fra-1 encoding a transcriptional factor activator protein 1 (AP-1) was identified. We have therefore investigated whether other members of the AP-1 transcription factor family might also be involved in renal carcinogenesis in the Eker rat model. In the present study, overexpression of fra-1, fra-2, c-jun, junB, and junD mRNAs was demonstrated in RCs by Northern blot analysis. Interestingly, AP-1 proteins were highly expressed even in the earliest preneoplastic lesions (e.g., phenotypically altered tubules) as suggested by immunohistochemistry. Moreover, 12-O-tetradecanoylphorbol-13-acetate-responsive element (TRE)-binding activity of AP-1 proteins was observed in RC cell extracts by electrophoretic mobility shift assay. As a next step, we transfected antisense oligonucleotides targeting AP-1 genes into RC cells and demonstrated that their growth was strongly inhibited. Thus, the data suggest that overexpression of AP-1 genes might play a crucial role in renal carcinogenesis in the Eker rat model.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
renal carcinoma  ISOFosl1 (Rattus norvegicus)2293758; 2293758mRNA:increased expression:kidneyRGD 
renal carcinoma  ISOFosl2 (Rattus norvegicus)2293758; 2293758mRNA:increased expression:kidneyRGD 
renal carcinoma  IEP 2293758; 2293758; 2293758; 2293758; 2293758mRNA:increased expression:kidneyRGD 
renal carcinoma  ISOJun (Rattus norvegicus)2293758; 2293758mRNA:increased expression:kidneyRGD 
renal carcinoma  ISOJunb (Rattus norvegicus)2293758; 2293758mRNA:increased expression:kidneyRGD 
renal carcinoma  ISOJund (Rattus norvegicus)2293758; 2293758mRNA:increased expression:kidneyRGD 

Objects Annotated

Genes (Rattus norvegicus)
Fosl1  (FOS like 1, AP-1 transcription factor subunit)
Fosl2  (FOS like 2, AP-1 transcription factor subunit)
Jun  (Jun proto-oncogene, AP-1 transcription factor subunit)
Junb  (JunB proto-oncogene, AP-1 transcription factor subunit)
Jund  (JunD proto-oncogene, AP-1 transcription factor subunit)

Genes (Mus musculus)
Fosl1  (fos-like antigen 1)
Fosl2  (fos-like antigen 2)
Jun  (jun proto-oncogene)
Junb  (jun B proto-oncogene)
Jund  (jun D proto-oncogene)

Genes (Homo sapiens)
FOSL1  (FOS like 1, AP-1 transcription factor subunit)
FOSL2  (FOS like 2, AP-1 transcription factor subunit)
JUN  (Jun proto-oncogene, AP-1 transcription factor subunit)
JUNB  (JunB proto-oncogene, AP-1 transcription factor subunit)
JUND  (JunD proto-oncogene, AP-1 transcription factor subunit)


Additional Information