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[Cancer Research 50, 3748-3753, June 15, 1990]
© 1990 American Association for Cancer Research
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Programmed Cell Death during Regression of PC-82 Human Prostate Cancer following Androgen Ablation1

Natasha Kyprianou, Hugh F. English and John T. Isaacs2

The Johns Hopkins Oncology Center, Baltimore, Maryland 21205 [N. K., J. T. I.], and the Divisions of Endocrinology and Urology, Hershey Medical Center, Hershey, Pennsylvania 17033 [H. F. E.]

To study the mechanism of regression of human prostatic cancer following androgen ablation, the androgen-responsive PC-82 human prostatic adenocarcinoma xenograft was used as a model system. Castration of male nude mice bearing PC-82 xenografts results in a 50% tumor regression by 2 wk following androgen ablation. This regression is due to a sequence of biochemical and morphological events that results in both the cessation of cell proliferation and activation of programmed death or apoptosis of the androgen-dependent prostatic cancer cells. Associated with this response are an enhanced expression of the transforming growth factor ß1 gene, a potent inhibitor of cell proliferation, and testosterone-repressed prostatic message 2 (designated TRPM-2), a programmed cell death-associated gene. Fragmentation of tumor DNA into nucleosomal oligomers and histological appearance of apoptotic bodies are characteristic early events that preceded the dramatic reduction in tumor volume following androgen ablation. These results suggest that androgen-dependent human prostatic cancer cells, like normal prostatic cells, retain the ability to inhibit proliferation and to activate programmed cell death in response to androgen ablation. Clarification of the biochemical pathway involved in the activation of this programmed cell death should identify new targets of therapy for even androgen-independent human prostatic cancer.

1 This investigation was supported by NIH Grants CA 50601 and CA 40011.

2 To whom requests for reprints should be addressed.

Received 12/18/89. Revised 2/28/90.


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