A transgenic strategy for analyzing the regulatory regions of the human prostate-specific antigen gene: potential applications for the treatment of prostate cancer (Review).

  • Authors:
    • R A Willis
    • C Wei
    • M J Turner
    • B P Callahan
    • A E Pugh
    • R K Barth
    • E M Lord
    • J G Frelinger
  • View Affiliations

  • Published online on: February 1, 1998     https://doi.org/10.3892/ijmm.1.2.379
  • Pages: 379-465
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Prostate-specific antigen (PSA) has been used clinically as a marker for the diagnosis and staging of prostate cancer due to its specific expression in prostate epithelial cells. In addition to its medical importance, its complex hormonal and tissue-specific regulation makes it an attractive model to study gene regulation. Two approaches have been applied to the identification of regulatory regions which confer this specific expression pattern. In vitro analysis of the regulatory regions of the human PSA gene using promoter reporter constructs and tumor cell lines has revealed a number of the DNA sequences involved in the hormone-dependent expression of PSA. We have pursued an alternative in vivo approach using transgenic animal technology, which is the focus of this review. Using this second approach, a transgenic mouse was generated using a 14 kilobase (kb) region of the human PSA gene encompassing the coding region and intervening sequences as well as 6 kb of upstream sequence and 2 kb of downstream sequence. This genomic DNA clone confers a PSA expression pattern in mice which appears to be very similar if not identical to that of humans, allowing us to investigate tissue-specificity and developmental regulation of PSA expression. In addition, these mice, for which PSA is a self-antigen, provide a model to test the feasibility and efficacy of PSA-directed immunotherapy for prostate cancer. The further identification of the PSA regulatory regions important for tissue-specificity may ultimately allow the design of new therapeutics for the treatment of prostate cancer.

Related Articles

Journal Cover

Feb 1998
Volume 1 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Willis R, Wei C, Turner M, Callahan B, Pugh A, Barth R, Lord E and Frelinger J: A transgenic strategy for analyzing the regulatory regions of the human prostate-specific antigen gene: potential applications for the treatment of prostate cancer (Review).. Int J Mol Med 1: 379-465, 1998
APA
Willis, R., Wei, C., Turner, M., Callahan, B., Pugh, A., Barth, R. ... Frelinger, J. (1998). A transgenic strategy for analyzing the regulatory regions of the human prostate-specific antigen gene: potential applications for the treatment of prostate cancer (Review).. International Journal of Molecular Medicine, 1, 379-465. https://doi.org/10.3892/ijmm.1.2.379
MLA
Willis, R., Wei, C., Turner, M., Callahan, B., Pugh, A., Barth, R., Lord, E., Frelinger, J."A transgenic strategy for analyzing the regulatory regions of the human prostate-specific antigen gene: potential applications for the treatment of prostate cancer (Review).". International Journal of Molecular Medicine 1.2 (1998): 379-465.
Chicago
Willis, R., Wei, C., Turner, M., Callahan, B., Pugh, A., Barth, R., Lord, E., Frelinger, J."A transgenic strategy for analyzing the regulatory regions of the human prostate-specific antigen gene: potential applications for the treatment of prostate cancer (Review).". International Journal of Molecular Medicine 1, no. 2 (1998): 379-465. https://doi.org/10.3892/ijmm.1.2.379