Abstract

Gene Discovery- Immunotherapy has been most successful when targeted to differentiation antigens expressed on hematopoietic tumors in large part because the target antigens are not expressed on essential cells or organs. Other cancers in which this approach could be successful are prostate, breast and ovary. To identify target antigens in prostate and breast cancers we have developed a computer based method to search the EST data base for ESTs that are expressed in prostate or breast cancer and not in other essential organs or cells. We have validated this approach experimentally and used it to identify several genes/proteins expressed in prostate cancer and not in essential normal organs. These include TARP, PAGE4, and GDEP. TARP is a mitochondrial protein that is also expressed in breast cancer. In the past year we have identified a new gene NGEP expressed in prostate and prostate cancer, encoding a membrane protein with seven membrane-spanning domains. We also identified POTE, a large gene family, expressed in prostate, ovary, testis, placenta and many cancers. We have prepared polyclonal and monoclonal antibodies to both these proteins and are using them to determine their cellular location and tissue expression patterns. We have also identified a new gene highly expressed in breast cancers (BPSR) and have produced antibodies to determine in which cells it is expressed. Preliminary results show very high expression in most breast cancers.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010298-08
Application #
7291831
Study Section
(LMB)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2005
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Sathyanarayana, Bangalore K; Hahn, Yoonsoo; Patankar, Manish S et al. (2009) Mesothelin, Stereocilin, and Otoancorin are predicted to have superhelical structures with ARM-type repeats. BMC Struct Biol 9:1
Ise, Tomoko; Das, Sudipto; Nagata, Satoshi et al. (2008) Expression of POTE protein in human testis detected by novel monoclonal antibodies. Biochem Biophys Res Commun 365:603-8
Levitin, Fiana; Weiss, Mordechai; Hahn, Yoonsoo et al. (2008) PATE gene clusters code for multiple, secreted TFP/Ly-6/uPAR proteins that are expressed in reproductive and neuron-rich tissues and possess neuromodulatory activity. J Biol Chem 283:16928-39
Epel, Malka; Carmi, Irit; Soueid-Baumgarten, Sharon et al. (2008) Targeting TARP, a novel breast and prostate tumor-associated antigen, with T cell receptor-like human recombinant antibodies. Eur J Immunol 38:1706-20
Bera, Tapan K; Saint Fleur, Ashley; Ha, Duc et al. (2008) Selective POTE paralogs on chromosome 2 are expressed in human embryonic stem cells. Stem Cells Dev 17:325-32
Das, Sudipto; Hahn, Yoonsoo; Walker, Dawn A et al. (2008) Topology of NGEP, a prostate-specific cell:cell junction protein widely expressed in many cancers of different grade level. Cancer Res 68:6306-12
Das, Sudipto; Ise, Tomoko; Nagata, Satoshi et al. (2007) Palmitoylation of POTE family proteins for plasma membrane targeting. Biochem Biophys Res Commun 363:751-6
Yokokawa, Junko; Bera, Tapan K; Palena, Claudia et al. (2007) Identification of cytotoxic T-lymphocyte epitope(s) and its agonist epitope(s) of a novel target for vaccine therapy (PAGE4). Int J Cancer 121:595-605
Das, Sudipto; Hahn, Yoonsoo; Nagata, Satoshi et al. (2007) NGEP, a prostate-specific plasma membrane protein that promotes the association of LNCaP cells. Cancer Res 67:1594-601
Egland, Kristi A; Liu, Xiu Fen; Squires, Stephen et al. (2006) High expression of a cytokeratin-associated protein in many cancers. Proc Natl Acad Sci U S A 103:5929-34

Showing the most recent 10 out of 24 publications