References
Query Results -- Details
MGI Accession ID: MGI:3784638
J Number: J:133908
Other Accession IDs:
Title: Deletion of PSCA increases metastasis of TRAMP-induced prostate tumors without altering primary tumor formation.
Authors: Moore ML; Teitell MA; Kim Y; Watabe T; Reiter RE; Witte ON; Dubey P
Journal: Prostate
Volume: 68
Issue: 2
Date: 2008 Feb 1
Year: 2008
Pages: 139-51
Review Status: Peer Reviewed
Abstract:
BACKGROUND: Prostate stem cell antigen (PSCA) is expressed in normal epithelium of various tissues, in embryos and adult animals. PSCA expression is upregulated in up to 70% of prostate tumors and metastases, and a subset of bladder and pancreatic cancers. However, its function is unknown. We studied the effect of targeted gene deletion of PSCA on normal organ development and prostate carcinogenesis. METHODS: PSCA +/+, PSCA +/-, and PSCA -/- mice were bred and aged to 22 months. A cohort of animals was treated with gamma-irradiation at 2 and 6 months of age. PSCA knockout mice were crossed to TRAMP mice and TRAMP+ PSCA +/+, TRAMP+ PSCA +/-, and TRAMP+ PSCA -/- mice and offspring aged to 10 months of age. Tissues were analyzed by RT-PCR, histology, and immunohistochemistry for markers of proliferation, apoptosis, angiogenesis, and tumor progression. RESULTS: PSCA knockout animals were viable, fertile and indistinguishable from wild-type littermates. Spontaneous or radiation-induced primary epithelial tumor formation was also similar in wild-type and PSCA knockout mice. We observed an increased frequency of metastasis in TRAMP+ PSCA heterozygous and knockout mice, compared to TRAMP+ wild-type mice. Metastases were largely negative for PSCA and androgen receptor. Cleaved-caspase 3 and CD31 staining was similar in all genotypes. Aurora-A and Aurora-B kinases were detected in the cytoplasm of PSCA heterozygous and knockout tumors, suggesting aberrant kinase function. CONCLUSION: These data suggest that PSCA may play a role in limiting tumor progression in certain contexts, and deletion of PSCA may promote tumor migration and metastasis.
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