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

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

doi:10.1038/2048

Cited by 166 publications

(132 citation statements)

References 8 publications

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“…Thompson and coworkers have consistently demonstrated that caveolin-1 expression was associated with progression of human prostate cancer and with primary and metastatic human breast cancer (Nasu et al, 1998;Thompson et al, 1999;Yang et al, 1999Yang et al, , 2000Li et al, 2001;Tahir et al, 2001). Recently the role of caveolin-1 as a tumor promoting factor in prostate cancer epithelial cells has been definitively addressed in vivo using the TRAMP mice model, which is analogous to human prostate tumors (Williams et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation

et al. 2006

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Progestin regulation of gene expression was assessed in the progestin-dependent murine tumor line C4HD which requires MPA, a synthetic progestin, for in vivo growth and expresses high levels of progesterone receptor (PR). By using suppressive subtractive hybridization, caveolin-1 was identified as a gene whose expression was increased with in vivo MPA treatment. By Northern and Western blot analysis, we further confirmed that caveolin-1 mRNA and protein expression increased in MPA-treated tumors as compared with untreated tumors. When primary cultures of C4HD cells were treated in vitro with MPA, caveolin-1 levels also increased, effect that was abolished by pre-treatment with progestin antagonist RU486. In addition, MPA promoted strong caveolin-1 promoter transcriptional activation both in mouse and human breast cancer cells. We also showed that MPA regulation of caveolin-1 expression involved in activation of two signaling pathways: MAPK and PI-3K. Short-term MPA treatment of C4HD cells led to tyrosine phosphorylation of caveolin-1 protein, where Src was the kinase involved. Additionally, we showed that MPA-induced association of caveolin-1 and PR, which was detected by coimmunoprecipitation and by confocal microscopy. Finally, we proved that MPA-induced proliferation of C4HD cells was inhibited by suppression of caveolin-1 expression with antisense oligodeoxynucleotides to caveolin-1 mRNA. Furthermore, we observed that inhibition of caveolin-1 expression abrogated PR capacity to induced luciferase activity from a progesterone response elementdriven reporter plasmid. Comprehensively, our results demonstrated for the first time that caveolin-1 expression is upregulated by progestin in breast cancer. We also demonstrated that caveolin-1 is a downstream effector of MPA that is partially responsible for the stimulation of growth of breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation

et al. 2006

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“…In vitro, in prostate cancer cells, Caveolin-1 specific anti-sense constructs induce cell death after testosterone removal. This effect was abrogated, when the cells were treated with the general caspase inhibitor Z-VAD-FMK [139]. Additionally, in human prostate cancer cells, Caveolin-1 presence favors phenylephrine-induced resistance to thapsigargin mediated cell death.…”

Section: Caveolin-1 and Drug-resistancementioning

confidence: 90%

The Caveolin-1 Connection to Cell Death and Survival

Quest

Lobos-González²,

Núñez³

et al. 2013

Current Molecular Medicine

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Abstract:Caveolins are a family of membrane proteins required for the formation of small plasma membrane invaginations called caveolae that are implicated in cellular trafficking processes. In addition to this structural role, these scaffolding proteins modulate numerous intracellular signaling pathways; often via direct interaction with specific binding partners. Caveolin-1 is particularly well-studied in this respect and has been attributed a large variety of functions. Thus, Caveolin-1 also represents the best-characterized isoform of this family with respect to its participation in cancer. Rather strikingly, available evidence indicates that Caveolin-1 belongs to a select group of proteins that function, depending on the cellular settings, both as tumor suppressor and promoter of cellular traits commonly associated with enhanced malignant behavior, such as metastasis and multi-drug resistance. The mechanisms underlying such ambiguity in Caveolin-1 function constitute an area of great interest. Here, we will focus on discussing how Caveolin-1 modulates cell death and survival pathways and how this may contribute to a better understanding of the ambiguous role this protein plays in cancer.

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“…Liganddependent Activation-High levels of caveolin-1 expression have been observed to correlate with the sensitivity of murine metastatic prostate cancer cells to androgen withdrawal (12), a finding that suggests caveolin plays a role in AR signaling. To test this hypothesis, we used a cell culture model to determine whether changes in the levels of caveolin-1 expression alter ligand-dependent AR activation.…”

Section: Overexpression Of Caveolin-1 Enhances Ar-mediated Transcriptmentioning

confidence: 98%

“…Ectopic overexpression of caveolin-1 inhibits Her2/Neu activity in vivo, a further suggestion of a tumor suppressor role of caveolin-1 (26). In cells derived from an mouse prostate reconstitution model, however, overexpression of caveolin-1 promotes resistance to apoptosis induced by androgen withdrawal, suggesting a promoter role of caveolin-1 in prostate tumor progression (12). Steroid hormone estrogen receptors have been shown to be potentiated by caveolin-1 in their transcriptional activities (27).…”

mentioning

confidence: 99%

“…They found, in samples from patients with prostate cancer, a positive correlation between expression of caveolin-1 and progression of the cancer (9). Using tumor cells derived from the mouse prostate reconstitution model (10,11), these authors link the expression of caveolin-1 to androgen sensitivity in hormone-resistant metastatic prostate cancer (12). Moreover, immunohistochemical staining of caveolin-1 in tumor samples from patients who had undergone radical prostatectomy suggested that caveolin-1 immunostaining is an independent predictor of disease progression (13).…”

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confidence: 99%

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Caveolin-1 Interacts with Androgen Receptor

Lu¹,

Schneider

Zheng³

et al. 2001

Journal of Biological Chemistry

213

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Androgen receptor (AR) belongs to the steroid hormone nuclear receptor superfamily. It functions as an androgen-dependent transcriptional factor that regulates genes for cell proliferation and differentiation. Caveolin is a principal component of caveolae membranes serving as a scaffold protein of many signal transduction pathways. Recent results correlate caveolin-1 expression with androgen sensitivity in murine prostate cancer. Furthermore, immunohistochemical staining of patient specimens suggests that caveolin expression may be an independent predictor of progression of prostate cancer. In this study, we investigate the potential interactions between AR signaling and caveolin-1 and demonstrate that overexpression of caveolin-1 potentiates ligand-dependent AR activation. Conversely, down-regulation of caveolin-1 expression by a caveolin-1 antisense expression construct can downregulate ligand-dependent AR activation. Association between these two molecules is also demonstrated by co-localization of AR with caveolin-rich, low-density membrane fractions isolated by an equilibrium sucrose gradient centrifugation method. Co-immunoprecipitation and glutathione S-transferase fusion protein pulldown experiments demonstrate that interaction between AR and caveolin-1 is an androgen-dependent process, offering further evidence for a physiological role of this interaction. Using a mammalian two-hybrid assay system, we determine that the NH 2 terminus region of caveolin-1 is responsible for the interaction with both the NH 2 -terminal domain and the ligand-binding domain of AR.

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

Cited by 166 publications

References 8 publications

Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation

Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation

The Caveolin-1 Connection to Cell Death and Survival

Caveolin-1 Interacts with Androgen Receptor

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