Elsevier

Genomics

Volume 73, Issue 3, 1 May 2001, Pages 243-254
Genomics

Regular Article
A Tissue-Specific Enhancer of the Prostate-Specific Membrane Antigen Gene, FOLH1

https://doi.org/10.1006/geno.2000.6446Get rights and content

Abstract

Prostate-specific membrane antigen (PSMA) is an integral membrane protein that is highly expressed on the surface of prostate epithelial cells. It is also expressed on the vascular endothelium of a number of tumor types. We have used an enhancer trap approach with randomly cleaved overlapping DNA fragments from an approximately 55-kb P1 cosmid insert encompassing the 5′ half and upstream sequences of the PSMA gene (FOLH1) to isolate an enhancer that strongly activates the FOLH1 core promoter region. The enhancer (PSME) is located in the third intron about 12 kb downstream from the start site of transcription and is characterized by a 72-bp direct repeat within a 331-bp core region. The PSME activates transcription from its own and heterologous promoters in prostate cell lines; enhancement is greatest in the PSMA-expressing cell line LNCaP (>250-fold). The PSME shows essentially no activity in five nonprostate cell lines. PSME-enhanced expression is repressed in the presence of androgen, mimicking the repression of the endogenous FOLH1 gene. The data demonstrate that both cell-type specificity and androgen regulation are intrinsic properties of the enhancer. These properties make the PSME an excellent candidate for regulation of gene expression in gene therapy approaches to prostate cancer.

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    Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession No. AF007544.

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    To whom correspondence should be addressed. Telephone: 61 2 9490 5168. Fax: 61 2 9490 5005. E-mail: [email protected].

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