<i>GDEP</i>, a new gene differentially expressed in normal prostate and prostate cancer†

Olsson, Pär; Bera, Tapan K.; Essand, Magnus; Kumar, Vasantha; Duray, Paul H.; Vincent, James J.; Lee, Byung Kook; Pastan, Ira

doi:10.1002/pros.1102

Cited by 29 publications

(28 citation statements)

References 11 publications

(14 reference statements)

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“…In situ hybridization of PATE mRNA on prostate cancer tissues was performed as described earlier (6,8). Biotinylated probes were prepared by using PATE (1,500 bp) and U6 (250 bp) cDNA cloned in pBluescript II SK(ϩ) plasmid, using the BioNick Labeling System kit (Life Technologies, Gaithersburg, MD) according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…To achieve this goal, we have focused on the identification of new, tissuespecific antigens by using the expressed sequence tag (EST) database to generate clusters of ESTs that are expressed in normal prostate and͞or prostate cancer but not in essential human tissues (1). Using this approach, we previously have identified several genes whose transcripts are expressed specifically in normal prostate and͞or prostate cancer (2)(3)(4)(5)(6). Using the same approach, we describe here another gene that is expressed specifically in prostate cancer, normal prostate, and testis.…”

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confidence: 99%

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PATE,a gene expressed in prostate cancer, normal prostate, and testis, identified by a functional genomic approach

Bera

Maitra

Iavarone

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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To identify target antigens for prostate cancer therapy, we have combined computer-based screening of the human expressed sequence tag database and experimental expression analysis to identify genes that are expressed in normal prostate and prostate cancer but not in essential human tissues. Using this approach, we identified a gene that is expressed specifically in prostate cancer, normal prostate, and testis. The gene has a 1.5-kb transcript that encodes a protein of 14 kDa. We named this gene PATE (expressed in prostate and testis). In situ hybridization shows that PATE mRNA is expressed in the epithelial cells of prostate cancers and in normal prostate. Transfection of the PATE cDNA with a Myc epitope tag into NIH 3T3 cells and subsequent cell fractionation analysis shows that the PATE protein is localized in the membrane fraction of the cell. Analysis of the amino acid sequence of PATE shows that it has structural similarities to a group of proteins known as three-finger toxins, which includes the extracellular domain of the type ␤ transforming growth factor receptor. Restricted expression of PATE makes it a potential candidate for the immunotherapy of prostate cancer.immunotherapy ͉ cancer vaccine ͉ snake toxin ͉ membrane protein P rostate cancer is the most frequently diagnosed noncutaneous cancer and the second leading cause of cancer deaths in men. It has been estimated that about one in five men in the United States will develop prostate cancer during their lifetime, and, to date, there are no curative therapies available for this disease after it has metastasized from its site of origin.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

PATE,a gene expressed in prostate cancer, normal prostate, and testis, identified by a functional genomic approach

Bera

Maitra

Iavarone

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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“…Several genes with specific or differential expression in prostate have been identified by this approach but none are membrane proteins (13)(14)(15)(16)(17)(18). In this report, we describe an additional gene that is specifically expressed in prostate cancer and in normal prostate but not in any other tissues.…”

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confidence: 91%

NGEP, a gene encoding a membrane protein detected only in prostate cancer and normal prostate

Bera

Das

Maeda

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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We identified a gene (NGEP) that is expressed only in prostate cancer and normal prostate. The two NGEP transcripts are 0.9 kb and 3.5 kb in size and are generated by a differential splicing event. The short variant (NGEP-S) is derived from four exons and encodes a 20-kDa intracellular protein. The long form (NGEP-L) is derived from 18 exons and encodes a 95-kDa protein that is predicted to contain seven-membrane-spanning regions. In situ hybridization shows that NGEP mRNA is localized in epithelial cells of normal prostate and prostate cancers. Immunocytochemical analysis of cells transfected with NGEP cDNAs containing a Myc epitope tag at the carboxyl terminus shows that the protein encoded by the short transcript is localized in the cytoplasm, whereas the protein encoded by the long transcript is present on the plasma membrane. Because of its selective expression in prostate cancer and its presence on the cell surface, NGEP-L is a promising target for the antibody-based therapies of prostate cancer.

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“…Identification of new tumor-specific antigens is an essential step for the successful development of immunotherapy ap- [12][13][14]. One of these, T cell receptor gamma alternate reading frame protein (TARP), is expressed on breast and prostate cancer cells [15,16].…”

Section: Introductionmentioning

confidence: 99%

Targeting TARP, a novel breast and prostate tumor‐associated antigen, with T cell receptor‐like human recombinant antibodies

et al. 2008

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MHC class I molecules are important components of immune surveillance. There are no available methods to directly visualize and determine the quantity and distribution of MHC/ peptide complexes on individual cells or to detect such complexes on antigen-presenting cells in tissues. MHC-restricted recombinant antibodies with the same specificity of T cell receptors (TCR) may become a valuable tool to address these questions. They may also serve as valuable targeting molecules that mimic the specificity of cytotoxic T cells. We isolated by phage display a panel of human recombinant Fab antibodies with peptidespecific, MHC-restricted TCR-like reactivity directed toward HLA-A2-restricted T cell epitopes derived from a novel antigen termed TCRc alternative reading frame protein (TARP) which is expressed on prostate and breast cancer cells. We have characterized one of these recombinant antibodies and demonstrated its capacity to directly detect specific HLA-A2/ TARP T cell epitopes on antigen-presenting cells that have complexes formed by naturally occurring active intracellular processing of the antigen, as well as on the surface of tumor cells. Moreover, by genetic fusion we armed the TCR-like antibody with a potent toxin and demonstrated that it can serve as a targeting moiety killing tumor cells in a peptide-specific, MHC-restricted manner similar to cytotoxic T lymphocytes. Key words: Immunotoxin Á MHC Á Recombinant antibody Á T-cell receptor IntroductionMost patients with metastatic prostate and breast cancers are provided with the limited benefits from standard chemo-and hormone-based therapies. During the recent years, much effort has been invested in developing new approaches, such as immunotherapy, to improve the therapeutic abilities, by combining the tumor specificity of cell-mediated immunity with the freedom from toxic chemotherapies.Recent immunotherapy approaches employ the principle that CD8 + CTL recognize and kill tumor cells that display peptides from tumor-associated antigens presented by MHC class I molecules. Several tumor antigens and HLA allele-specific peptides from prostate cancer-associated antigens have been identified as CD8 + T cell epitopes, including HLA-A2-binding peptides derived from prostate-specific antigen (PSA) [1,2], prostate-specific membrane antigen (PSMA) [3], prostate stem cell antigen (PSCA) [4,5], and prostate acid phosphatase 6, which are all now components of current vaccine trials [5][6][7][8][9][10][11].Identification of new tumor-specific antigens is an essential step for the successful development of immunotherapy ap- [12][13][14]. One of these, T cell receptor gamma alternate reading frame protein (TARP), is expressed on breast and prostate cancer cells [15,16]. It was shown that TARP was expressed on >90% of cancer specimens examined [9,15]. In order to define new breast and prostate CD8 + T cell tumor antigens, two wild-type HLA-A2 epitopes from TARP were identified [17]. The wild-type sequences were also improved by sequence modifications to produce epitopeenha...

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GDEP, a new gene differentially expressed in normal prostate and prostate cancer†

Abstract: Our data proves that tissue specific genes can be identified by EST database mining. The prostate specificity of GDEP expression indicates that GDEP may be useful in the diagnosis or treatment of prostate cancer. Published 2001 Wiley-Liss, Inc.

Cited by 29 publications

References 11 publications

PATE,a gene expressed in prostate cancer, normal prostate, and testis, identified by a functional genomic approach

PATE,a gene expressed in prostate cancer, normal prostate, and testis, identified by a functional genomic approach

NGEP, a gene encoding a membrane protein detected only in prostate cancer and normal prostate

Targeting TARP, a novel breast and prostate tumor‐associated antigen, with T cell receptor‐like human recombinant antibodies

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