Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells

Yasutomo Nasu, Terry L. Timme, Guang Yang, Chris H. Bangma, Likun Li, Chengzhen Ren, Sang Hee Park, Marlene DeLeon, Jianxiang Wang, Timothy C. Thompson

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163 Citations (Scopus)

Abstract

Although prostate cancer cells are often initially sensitive to androgen ablation, they eventually lose this response and continue to survive, grow and spread in the absence of androgenic steroids. The mechanism(s) that underlie resistance to androgen ablation therapy remain mostly unknown. We have demonstrated that elevated caveolin protein levels are associated with human prostate cancer progression in pathological specimens. Here we show that suppression of caveolin expression by a stably transfected antisense caveolin-1 cDNA vector converted androgen-insensitive metastatic mouse prostate cancer cells to an androgen-sensitive phenotype. Orthotopically grown tumors and low-density cell cultures derived from antisense caveolin clones had increased apoptosis in the absence of androgenic steroids, whereas similarly grown tumors and cells from vector (control) clones and parental cells were not sensitive to androgens. Studies using a representative antisense caveolin clone showed that selection for androgen resistance in vivo correlated with increased caveolin levels, and that adenovirus-mediated caveolin expression blocked androgen sensitivity. Our results identify a new candidate gene for hormone-resistant prostate cancer in man and indicate that androgen insensitivity can be an inherent property of metastatic prostate cancer.

Original languageEnglish
Pages (from-to)1062-1064
Number of pages3
JournalNature Medicine
Volume4
Issue number9
DOIs
Publication statusPublished - Sep 1998

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Nasu, Y., Timme, T. L., Yang, G., Bangma, C. H., Li, L., Ren, C., Park, S. H., DeLeon, M., Wang, J., & Thompson, T. C. (1998). Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells. Nature Medicine, 4(9), 1062-1064. https://doi.org/10.1038/2048