High expression of a specific T-cell receptor γ transcript in epithelial cells of the prostate

Essand, Magnus; Vasmatzis, George; Brinkmann, Ulrich; Duray, Paul H.; Lee, Byung Kook; Pastan, Ira

doi:10.1073/pnas.96.16.9287

Cited by 58 publications

(74 citation statements)

References 17 publications

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“…In a recent study, no evidence for TCRab or TCRd transcripts or proteins was found in epithelial tumor cells, whereas, a partial TCRg chain mRNA, lacking the V region was detected. This mRNA encodes a 7 kDa nuclear protein, TARP, which is translated from an alternate reading frame and is therefore not homologous to the TCRg protein (Essand et al, 1999;Wolfgang et al, 2000). By contrast, the identi®cation of a cell surface antigen on mesenchymal cells identi®ed by an antibody to the TCR constant region suggests that the truncated TCRb mRNA may encode a protein which is translated from a reading frame identical to that found in T cells.…”

Section: Discussionmentioning

confidence: 98%

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The mesenchyme expresses T cell receptor mRNAs: relevance to cell growth control

et al. 2002

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The mesenchyme plays a crucial regulatory role in organ formation and maintenance. However, comprehensive molecular characterization of these cells is lacking. We found unexpectedly that primary mesenchyme, as well as mesenchymal cell clones, express T cell receptor (TCR)ab mRNAs, lacking the variable region. Immunological and genetic evidence support the expression of a corresponding TCRb protein. Additionally, mRNAs encoding TCR complex components including CD3 and z chain are present. A relatively higher expression of the mesenchymal TCRb mRNA by cultured mesenchymal cell clones correlates with fast growth, whereas poorly expressing cells are slow growers and are contact inhibited. The clones that express relatively higher amount of the TCR mRNA exhibit an increased capacity to form tumors in nude mice. However, the expression of this mRNA in the mesenchyme is not per se leading to tumorigenesis, as demonstrated by primary mesenchyme that does not form tumors in mice while expressing moderate amounts of the TCR transcripts. The expression of mesencymal TCRb was con®ned to the G2/M phases of the cell cycle in the MBA-13 mesenchymal cell line. This cell cycle dependent expression, considered together with the correlation between growth properties and the level of TCR expression by cell clones, implies association of mesenchymal TCR with cell growth control.

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Section: Discussionmentioning

confidence: 98%

“…Recently, a TCRg mRNA translated from an alternate reading frame has been identi®ed in epithelial cells. The encoded protein is albeit distinct from TCRg (Essand et al, 1999;Wolfgang et al, 2000). It is therefore possible that the TCR gene family serves functions other than those already ascribed to it.…”

Section: Introductionmentioning

confidence: 99%

The mesenchyme expresses T cell receptor mRNAs: relevance to cell growth control

et al. 2002

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“…As a result of this understanding, new genes specifically expressed in human breast and prostate cancer have been identified recently by utilizing new gene discovery tools [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].…”

Section: Introductionmentioning

confidence: 99%

“…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].…”

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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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“…To achieve this goal, we focused on utilizing the EST database to generate clusters of ESTs that are expressed in normal prostate and/ or prostate cancer. Using this approach, we previously identified genes whose transcripts are specifically expressed in normal prostate and/or prostate cancer [3][4][5][6]. Using a similar approach, we describe here the cloning and characterization of Copine 8, a new member of the gene family that produces the calcium-dependent, phospholipid binding proteins called copines [7][8][9].…”

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confidence: 99%

Cloning, molecular characterization, and expression analysis of Copine 8

Maitra

Grigoryev

Bera

et al. 2003

Biochemical and Biophysical Research Communications

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Copines are ubiquitously expressed, phospholipid-binding proteins that have been conserved through evolution. In this paper, we report the cloning and molecular characterization of a new member of the Copine family, Copine 8. This gene has been isolated and characterized using a combination of bioinformatic and experimental approaches. Using an algorithm to cluster ESTs (expressed sequence tags) that are available through the public ''GoldenPath'' database, Copine 8 was initially identified as a gene predominantly expressed in prostate and testis. Cloning and molecular analysis revealed that this gene is expressed in low-levels in most tissues examined. Two different isoforms of this gene have been isolated. Strongest expression of Copine 8 mRNA is seen in the prostate, heart, and brain. Taken together, this data suggest that Copine 8 may have an important role to play in prostate regulation and development.

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High expression of a specific T-cell receptor γ transcript in epithelial cells of the prostate

Cited by 58 publications

References 17 publications

The mesenchyme expresses T cell receptor mRNAs: relevance to cell growth control

The mesenchyme expresses T cell receptor mRNAs: relevance to cell growth control

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

Cloning, molecular characterization, and expression analysis of Copine 8

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