Gene Discovery

Pastan, Ira

Abstract

Gene Discovery- Immunotherapy has been most successful when targeted to differentiation antigens expressed on hematopoietic tumors and melanomas 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. PAGE4 is a cytoplasmic protein and GDEP is a nuclear protein. We have discovered two new members of the MRP family, one of which (MRP9) is highly expressed in breast cancers. We have also developed an experimental approach to finding new immunotherapy targets in breast cancer by cloning new genes from membrane bound polysomal RNA. One of these that we have named BASE has the properties of a secreted protein and is found expressed in many breast cancers but only normal salivary gland. Base will be evaluated as a possible blood test for breast cancer.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: Division of Basic Sciences - NCI (NCI)
• Type: Intramural Research (Z01)
• Project #: 1Z01BC010298-06
• Application #: 6950991
• Study Section: (LMB)
• Support Year: 6
• Fiscal Year: 2003

Institution

• Name: Basic Sciences
• Country: United States

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