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Updated: Jun 23, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 19, 2013
Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate
1Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA.
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.
Insights
Prostate cancer cells can become resistant to androgen ablation therapy. Suppressing caveolin-1 protein levels restored androgen sensitivity in metastatic prostate cancer cells, suggesting caveolin-1 as a target for hormone-resistant prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Prostate cancer often becomes resistant to androgen ablation therapy.
- Mechanisms of androgen insensitivity in prostate cancer are largely unknown.
- Elevated caveolin protein levels correlate with prostate cancer progression.
Purpose of the Study:
- To investigate the role of caveolin in androgen insensitivity of prostate cancer.
- To determine if suppressing caveolin expression can restore androgen sensitivity.
Main Methods:
- Stable transfection of mouse prostate cancer cells with antisense caveolin-1 cDNA.
- Assessment of androgen sensitivity, apoptosis, and caveolin levels in vitro and in vivo.
- Adenovirus-mediated caveolin expression to study its effect on androgen sensitivity.
Main Results:
- Suppression of caveolin-1 expression converted androgen-insensitive cells to an androgen-sensitive phenotype.
- Antisense caveolin clones exhibited increased apoptosis in the absence of androgens.
- Increased caveolin levels correlated with androgen resistance in vivo.
- Adenovirus-mediated caveolin expression blocked androgen sensitivity.
Conclusions:
- Caveolin-1 plays a critical role in the development of androgen insensitivity in metastatic prostate cancer.
- Caveolin-1 is a potential therapeutic target for hormone-resistant prostate cancer.
- Androgen insensitivity may be an intrinsic characteristic of metastatic prostate cancer.
