RGD Reference Report - Expression of the F-box protein SKP2 induces hyperplasia, dysplasia, and low-grade carcinoma in the mouse prostate. - Rat Genome Database

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Expression of the F-box protein SKP2 induces hyperplasia, dysplasia, and low-grade carcinoma in the mouse prostate.

Authors: Shim, EH  Johnson, L  Noh, HL  Kim, YJ  Sun, H  Zeiss, C  Zhang, H 
Citation: Shim EH, etal., Cancer Res. 2003 Apr 1;63(7):1583-8.
RGD ID: 2315046
Pubmed: PMID:12670908   (View Abstract at PubMed)

Low or absent expression of the cyclin-dependent kinase inhibitor p27(Kip1) serves as an excellent malignant marker for prostate and other human cancers. The level of p27(Kip1) is regulated primarily by the ubiquitin E3 ligase SCF(SKP2) through ubiquitin-dependent proteolysis. Expression of the F-box protein SKP2 is inversely correlated with p27 in many cancers. To determine the role of SCF(SKP2) in proliferation and tumorigenesis, we established transgenic mouse lines that specifically expressed SKP2 in the prostate gland. Unscheduled expression of SKP2 promoted marked overproliferation, resulting in hyperplasia, dysplasia, and low-grade carcinoma in the prostate gland. Consistent with its critical role in p27 proteolysis, SKP2 expression caused significant down-regulation of p27 in prostate glands from transgenic animals. Immunohistological staining indicated that SKP2 expression is restricted to the hyperplastic/dysplastic regions and that there is an inverse relationship between SKP2 and p27 expression in the ductal epithelium in transgenic animals. The prostate glands from transgenic mice also exhibited high levels of proliferative and mitotic markers such as Ki67 and cyclin B1. Our data suggest that SKP2 acts as an oncoprotein in the mouse prostate gland, probably through its function as a limiting factor for ubiquitin-dependent degradation of p27.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Ccnb1  (cyclin B1)
Skp2  (S-phase kinase associated protein 2)

Genes (Mus musculus)
Ccnb1  (cyclin B1)
Skp2  (S-phase kinase-associated protein 2)

Genes (Homo sapiens)
CCNB1  (cyclin B1)
SKP2  (S-phase kinase associated protein 2)


Additional Information