Caveolin-1 mediates testosterone-stimulated survival/clonal growth and promotes metastatic activities in prostate cancer cells

L. Li, G. Yang, S. Ebara, T. Satoh, Y. Nasu, T. L. Timme, C. Ren, J. Wang, S. A. Tahir, T. C. Thompson

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Abstract

Previously, we demonstrated that up-regulation of caveolin-1 (cav-1) was associated with prostate cancer metastasis, biochemical recurrence after radical prostatectomy, and androgen insensitivity. The objective of this study was to characterize the regulation of cay-1 by testosterone (T) and to test the effects of cav-1 on prostate cancer cell survival/clonal growth and metastatic activities. Our results demonstrated that T upregulated cav-1 protein levels in part through transcriptional regulation and significantly enhanced survival of prostate cancer cell lines ABAC3 and LNCaP after serum starvation (>40% and >60% increased viability, respectively) and in an extended clonogenic assay (approximately 4-fold and 6-fold increase in colonies, respectively). Importantly, antisense cav-1 inhibited the survival effects of T in these assay systems. Modest but not high levels of adenoviral vector-mediated cav-1 expression alone also significantly increased viability (>40%) and clonal growth (10-fold increase in colonies) after serum starvation. Analysis of spontaneous metastasis in stably transfected antisense cav-1 mouse prostate cancer cell clones demonstrated reduction of spontaneous lymph node metastasis incidence (13%), spontaneous lymph node metastasis volume (46%), and experimental lung metastasis incidence (40%) compared with vector control cell clones. Surgical castration further reduced spontaneous lymph node metastasis incidence and volume (18% and 28%, respectively) in antisense cancer cell clones, but not in vector control clones. Our studies demonstrate that cav-1 is a downstream effector of T-mediated prostate cancer cell survival/clonal growth and that modest levels of cav-1 can independently promote prostate cancer cell survival/clonal growth and metastatic activities.

Original languageEnglish
Pages (from-to)4386-4392
Number of pages7
JournalCancer Research
Volume61
Issue number11
Publication statusPublished - Jun 1 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Li, L., Yang, G., Ebara, S., Satoh, T., Nasu, Y., Timme, T. L., Ren, C., Wang, J., Tahir, S. A., & Thompson, T. C. (2001). Caveolin-1 mediates testosterone-stimulated survival/clonal growth and promotes metastatic activities in prostate cancer cells. Cancer Research, 61(11), 4386-4392.