Molecular Targets for the Prevention of Prostate Cancer

Abstract

Abstract : The objectives of this proposal are to determine whether protein kinase C epsilon (PKCepsilon) is linked to the initiation and progression of Prostate cancer (PCa) and should be explored as a molecular target for the prevention of human PCa. PKCepsilon, a calcium-insensitive PKCepsilon, is among the PKCepsilon isoforms expressed in both mouse and human prostate tissue. We plan to test the hypothesis that PKCepsilon is linked to the onset, progression and metastasis PCa. Two specific aims are proposed to test this hypothesis. Specific Aim #1: To obtain the first molecular genetic evidence that PKCepsilon is linked to the development of PCa. To accomplish this specific aim, we will employ TRAMP mice, the well established mouse model of PCa. We will deplete PKCepsilon in TRAMP mice by crossbreeding TRAMP mice with PKCepsilon knockout (-/-) mice. We will evaluate TRAMP-PKCepsilon KO mice for the development and progression of PCa in vivo. We will determine whether the genetic loss of one (-/+) or both (-/-) PKCepsilon alleles will attenuate the progression of PCa. Specific Aim #2: To explore the mechanisms by which PKCepsilon may promote the progression of AI PCa. This report will review the accomplishments made over the first year of grant award with respect to these specific objectives and according to the time line proposed in the original statement of work of the project.