Dr. Ashwani K. Sood joined the staff of Roswell Park Cancer Institute in 1983 as a cancer research scientist in the Department of Immunology. In 2001 he was named as assistant member of the department. He also participates as a faculty member with the University at Buffalo. Previous to joining RPCI he was a member of the Department of Human Genetics at Yale University.
Dr. Sood’s laboratory first reported that PDEF (prostate derived Ets factor, a member of the Ets family of transcription factors) is overexpressed in >70% of human breast tumors. Further, down regulation of PDEF reduces tumor cell survival in vitro and its transfection induces increased growth of breast epithelial cell lines in vitro and in immuno deficient mice. Moreover, elevated PDEF expression in primary tumors correlates with poor overall survival of breast cancer patients.
Together, these results showed that PDEF is a highly active novel oncogene in breast cancer. Additionally, PDEF expression is induced early in the precancerous ADH and DCIS lesions and maintained in invasive breast tumors and in lymph node metastases. These results provide a compelling rationale to evaluate PDEF as a target/antigen for primary prevention and treatment of breast cancer.
Towards this goal, we have found that immunization with Pse (prostate specific Ets, the mouse homolog of PDEF) induces specific T cell responses with anti-tumor activity in a mouse model of breast cancer. Moreover, we find that PDEF sequence contains three immunogenic peptides that induce specific T cell responses in HLA-A2/Kb transgenic mice in the context of HLA-A2. These results strongly support the development of PDEF based vaccines and T cell therapies for primary prevention and treatment of breast cancer.
Additionally, the mechanism(s) underlying the oncogenic action of PDEF in breast cancer remain poorly understood. Our studies on PDEF regulated genes identified CEACAM6 as a PDEF-induced molecule. Further characterization showed that similar to PDEF, CEACAM6 also has oncogenic role in breast cancer. These results provide further rationale for developing PDEF and CEACAM6 based vaccines and immunotherapies against breast cancer.
Ghadersohi A and Sood AK. Prostate epithelium-derived Ets transcription factor mRNA is over expressed inhuman breast tumors and is a candidate breast tumor marker and a breast tumor antigen. Clin. Cancer Res. 2001; 7:2731-2738.
Sood AK, Saxena R, Groth J, Desouki MM, Cheewakriangkrai C, Rodabaugh KJ, Kasyapa CS and Geradts J. Expression characteristics of PDEF support a role in breast and prostate cancer progression. Hum. Pathol. 2007; 38:1621-1627.
Sood AK, Wang J, Mhawech-Fauceglia P, Jana B, Liang P, Geradts J. Sam-pointed domain containing Ets transcription factor in luminal breast cancer pathogenesis. Cancer Epidemiol Biomar & Pev 2009; 18: 1899-1903.
Sood AK, Kim H and Geradts J. PDEF in prostate cancer. The Prostate. 2012; 72:592-596.
Mukhopadhyay A, Khoury T, Stein L, Shrikant P, Sood AK. Prostate derived Ets transcription factor and Carcinoembryonic antigen related cell adhesion molecule 6 constitute a highly active oncogenic axis in breast cancer. Oncotarget. 2013; 4:610-21.