Programmed cell death during regression of PC-82 human prostate cancer following androgen ablation

Natasha Kyprianou, Hugh F. English, John Tod Isaacs

Research output: Contribution to journalArticle

Abstract

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 β1 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.

Original languageEnglish (US)
Pages (from-to)3748-3753
Number of pages6
JournalCancer Research
Volume50
Issue number12
StatePublished - Jun 15 1990

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Androgens
Prostatic Neoplasms
Cell Death
Heterografts
Castration-Resistant Prostatic Neoplasms
Cell Proliferation
Orchiectomy
Transforming Growth Factors
DNA Fragmentation
Tumor Burden
Nude Mice
Genes
Testosterone
Neoplasms
Adenocarcinoma
Apoptosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Programmed cell death during regression of PC-82 human prostate cancer following androgen ablation. / Kyprianou, Natasha; English, Hugh F.; Isaacs, John Tod.

In: Cancer Research, Vol. 50, No. 12, 15.06.1990, p. 3748-3753.

Research output: Contribution to journalArticle

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