Each year more than one hundred thousand cases of prostate cancer have been diagnosed in the United States. Prostate cancer 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. 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. These anti-AR mAbs were developed using peptide fragments as immunogens, and they do not always stain tissue effectively or inhibit AR function. 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 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.Awardee's statement of the potential commercial applications of the research: The high affinity anti-androgen receptor mAbs and purified AR protein generated from this project may be used to stain paraffin imbedded tissue and can be used to develop sensitive and specific ELISA methods for detecting and quantifying AR protein in tissue samples. These methods also are applicable to detect anti-AR autoimmune antibodies in serum from patients with prostate diseases. The anti-AR mAbs with functional inhibition activity can be used by researchers to study mechanisms involved in androgen-induced hormone activation.National Cancer Institute (NCI)
