Kenneth V. Honn, Principal Investigator

Title:  Role of Thromboxane in Prostate Cancer Progression

P.I.: Kenneth V. Honn

Effort:  25%

Funding Agency – NIH/NCI -- Period – 08/15/06-07/31/11

Total Funding – $1,618,300

Description – The major goals of this project are: (1) Define the expression and function of TX synthase and TPs during prostate carcinogenesis using the TRAMP transgenic mouse model; (2) Characterize TXA2 receptors expressed in prostate cancer cells and elucidate how TXA2 signaling loop regulates tumor cell motility; (3) Study the functional role for TX synthase and TXA2 receptors in tumor formation, progression, and metastasis, and its relationship with hemostatic components, platelets in particular.

Title:   Characterization of a Novel 12(S)-HETE Receptor and Role in Prostate Cancer Progression

P.I.: Kenneth V. Honn

Effort:  10%

Funding Agency – DOD -- Period – 12/30/05-1/29/09

Total Funding – $565,398

Description – The major goals of this project are: (1) Characterize the biochemical properties of GPR31 as a 12(S)-HETE receptor; (2) Study the expression profile of GPR31 in invasion and tumor progression; (3) Study the roles of GPR31 in tumor survival and invasion by overexpressing GPR31 in DU145 cells and silencing GPR31 in PC3 cells.

Title:  Role of Eicosanoids in Tumor Cell Metastasis

P.I.: Kenneth V. Honn

Effort:  15%

Funding Agency – NIH/NCI -- Period – 4/07/04 - 3/31/09

Total Funding – $1,359,000

Description – The major goals of this project are: (1) Determine the structural basis for the interaction between beta4 integrin subunit and 12-LOX; (2) Study how alpha6beta4 regulates 12-LOX cellular localization and activity; (3) Determine whether 12-LOX regulates the function of alpha6beta4 in hemidesmosomes; (4) Study whether and how 12-LOX and beta4 integrin contribute to the survival of carcinoma cells; and (5) Determine whether and how 12-LOX and beta4 collaborate in carcinoma invasion in vitro and tumor progression in animal models. The proposed studies, when accomplished, will provide significant insights into eicosanoid regulation of tumor progression.

Title: 12-Lipoxygenase and Prostate Cancer Angiogenesis

P.I.: Kenneth V. Honn

Effort:  10%

Funding Agency – Fund for Cancer Research -- Period – 8/15/07 – 8/14/09

Total Funding - $75,000

Description - The aim of this project proposal is to elucidate the mechanisms and signal transduction pathways governing the regulation of VEGF expression by 12-LOX and 12(S)-HETE. Since VEGF expression is regulated differently under normoxic and hypoxic conditions of the tumor, our present proposal aims at delineating mechanisms, by which 12-LOX activates VEGF, under normoxia and hypoxic conditions. 

Title:  12-Lipoxygenase-Induced Prostate Cancer Angiogenesis and Resistance to Antiangiogenic Therapy

P.I.: Kenneth V. Honn

Effort:  10%

Funding Agency – Department of Defense -- Period – 9/1/08 – 8/31/11

Total Funding – $563,494

Description – The major goal of this project is to 1. Study the regulation of HIF-1α and Sp1 by 12-LOX and 12(S)-HETE in prostate cancer cells under normoxic and hypoxic conditions with focus on the signaling pathways involved.  2. Assess whether 12-LOX signals via HIF-1α to upregulate VEGF expression and secretion in prostate cancer cells under normoxic and hypoxic conditions; and identify the relative contributions of HIF-1 and Sp1.  3. Investigate mechanisms of resistance to anti-angiogenic agents imparted by 12-LOX.