ANTI-ANDROGEN RECEPTOR MABS FOR HUMAN PROSTATE CANCER

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Each year more than one hundred thousand cases of prostate cancer have been diagnosed in the United States and which is the first in solid tumor incidence and second in cancer related death in the American male population. Yet, the factors which are involved in prostate carcinogenesis, except for the presence of androgen, remain unclear. Recently, scientists have studied oncogene amplification and tumor suppressor gene expression in prostate tissue and failed to establish a relationship between the expression of these genes and prostate carcinogenesis. On the other hand, it has been shown that metastatic prostate cancer patients with higher pretreatment plasma testosterone levels tend to have a greater survival rate when receiving primary hormonal therapy than those patients with low testosterone levels at the time of diagnosis. Thus, the androgen and androgen receptor (AR) expression may play an important role during prostate carcinogenesis. Recently, the anti-AR monoclonal antibody (Mab) has become available which make the assessment of AR levels and their localization in tissues possible. However, these anti-AR Mabs were developed using merely peptide fragments as immunogens. Consequently, these Mabs do not always stain tissue effectively and do not react with AR functional domains. Thus, the application of these Mabs has been limited. In addition, the lack of high affinity anti-Ar mabs and purified human AR proteins has hampered the development of a convenient ELISA test for clinical applications. In this proposal we will focus on the production and purification of full-length AR proteins from insect cells infected with baculovirus vector carrying the AR gene; these proteins will be used as immunogens to produce high affinity anti-AR Mabs and develop immunoassays for the clinical applications in prostate cancer.