Transplantable human prostate cancer (PC-82) in athymic nude mice : a model for the study of androgen-regulated tumor growth

This thesis describes the characterization and further application of a model system for prostate cancer, the human prostatic adenocarcinoma PC-82 which is transplantable in athymic nude mice. The mortality rate of patients suffering from prostatic carcinoma is high, in spite of the high response rates which are initially achieved with hormonal treatment ofthese patients. Growth and function of the prostate are primarily dependent on androgenic stimuli. Hormonal treatment of prostatic carcinoma is based upon the suppression of the testicular production of androgens. This can be achieved directly by surgical removal of the testes or indirectly by inhibiting the hypophyseal gonadotropin release through treatment with estrogens or analogues of luteinizing hormone-releasing hormone (LHRH). However, in the majority of patients relapse of the tumor occurs following a favorable response to androgen-ablation therapy. Progression is caused mainly by a loss of androgen-sensitivity of the tumor. Since many investigations relevant to prostate cancer cannot be performed in patients, there is a great need for well-characterized model systems which reflect the properties of clinical prostate cancer. Relevant aspects of the prostate in general and of prostatic carcinoma in particular are described in chapter 1, which also contains a summary of the current knowledge of androgen action in the prostate and information on the available model systems for prostatic cancer.