We are interested in understanding the molecular mechanisms that underlie tumor growth, development, and metastasis. Dr. Nelson’s research focuses on three main areas: (i) inflammation and tumor progression/metastasis, (ii) racial disparities and cancer, (iii) molecular diagnosis of cancer and other genetic diseases. Our approach involves a combination of cell biology biochemistry, molecular biology, and whole animal models of cancer.
Chronic inflammation contributes to tumor progression and metastasis. Cyclooxygenase 2 (COX-2) over expression also strongly contributes to the growth and metastatic potential of colon cancer cells. COX-2 converts arachidonic acid to PGE2 which can affect neoplastic cell behavior by binding to one of four prostanoid EP receptors (EP1-4). Evidence is accumulating that PGE2/EP4 receptor signaling plays a functional role in colon carcinogenesis. We have initiated studies focused toward understanding how PGE2/EP4 receptor signaling contributes to the pathogenesis of cancer. We have previously demonstrated the following: 1) PGE2 stimulates colon cancer cell proliferation; 2) PGE2 via the EP4 receptor activates ERK and phosphorylates the transcription factor CREB which in turn leads to the induction of gene expression; 3) the EP4 receptor antagonist, L161, 982, blocks PGE2 induced signal transduction and colon cancer cell growth in vitro and in the chick embryo assay; 4) the EP4 receptor is aberrantly expressed in malignant colon cancer lesions and 5) S100P is a previously unidentified downstream target of PGE2/EP4 receptor signal transduction. We are using in vitro and in vivo model systems to examine how chronic inflammation contributes to specific stages of cancer.