Current research areas

• To identify genes whose expression is regulated by PDEF over expression and determine their role in breast cancer progression
• To determine the potential of PDEF and certain PDEF-induced proteins as targets of vaccine and antibody therapy of cancer

PDEF Belongs to Ets Family of Transcription Factors
The founding member of this family, i.e., the v-oncogene of E twenty six (ETS) retrovirus, causes leukemia in chickens. The Ets transcription factors are:

-Expressed across metazoan evolution; 27 members in man, 26 in mice, 10 in C elegans and 9 in Drosophila; They are characterized by a relatively conserved DNA binding domain (ETS-DBD) Bind GGAA/T core DNA sequence

-Self-inhibited, Activated by phosphorylation or by interaction with other TFs;  Their expression levels and interaction with other proteins determines their specificity for modulating gene expression.

-Many are expressed ubiquitously, some in hematopoetic cell lineage and others in epithelial cell lineage; Majority activate transcription, several repress transcription

-Ets transcription factors are downstream targets of RAS-MAPP signaling pathway.

Expression characteristics of PDEF support a role in cancer expression
Our work over the past several year has shown that: PDEF expression is frequently induced in human breast, ovarian and prostate cancers. Further, PDEF expression is highly restricted in normal human tissues that is primarily limited to normal prostate tissue with weaker expression in trachea. Relative to other epithelial specific Ets transcription factors including ESE-1, ESE-2 and ESE-3, PDEF shows preferential over expression in tumors from the hormonally sensitive tissues including breast, ovarian and prostate tumors. Additionally, PDEF cDNA transfection enhanced the tumor forming ability of MCF-12A breast cell line in immunodeficient mice. Together, these results support an important role for PDEF in the progression of breast, ovarian and prostate cancers.

How PDEF may promote tumor progression?

Our hypothesis is that certain genes regulated by PDEF encode proteins that positively feed back on the Ras-MAPK pathway as well as other pathways critical to tumor progression. A schematic outline of our hypothesis is shown at the right.