Programmed cell death during regression of PC-82 human prostate cancer following androgen ablation.
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 beta 1 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.
Kyprianou
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Johns Hopkins Oncology Center, Baltimore, Maryland 21205.
English
H F
HF
Isaacs
J T
JT
D000728:Androgens; D000818:Animals; D002369:Castration / Q000379:methods; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004273:DNA, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D011467:Prostate / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis*; D012074:Remission Induction; D013739:Testosterone; D013997:Time Factors; D015291:Transforming Growth Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000728:Androgens; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013739:Testosterone; D015291:Transforming Growth Factors