Androgen Deprivation Therapy as Primary Treatment for Prostate Cancer

Cannata, Dara; Kirschenbaum, Alexander; Levine, Alice C.

doi:10.1210/jc.2011-2353

Cited by 33 publications

(29 citation statements)

References 30 publications

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“…Patients with metastases are insensitive to conventional treatments, including androgen-deprivation, chemotherapy and radiotherapy [16,17]. For bone metastatic patients, bisphosphonates and denosumab, a human monoclonal antibody against receptor activator of nuclear factor κ-B ligand (RANKL) could inhibit bone resorption and improve bone density to relieve pain and tumor-induced hypercalcemia [18,19].…”

Section: Discussionmentioning

confidence: 99%

SUMO-Specific Cysteine Protease 1 Promotes Epithelial Mesenchymal Transition of Prostate Cancer Cells via Regulating SMAD4 deSUMOylation

Zhang¹,

Wang²,

Wang³

et al. 2017

IJMS

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In advanced prostate cancer, small ubiquitin-like modifier (SUMO)-specific cysteine protease 1 (SENP1) is up-regulated. However, the role of SENP1 in regulating deSUMOylation of TGF-β/SMADs signaling is unknown. In this study, we developed a lentiviral vector, PLKO.1-shSENP1, to silence SENP1 in prostate cancer cells with high metastatic characteristics (PC3M). Likewise, we also created an adenovirus vector, Ad5/F11p-SENP1 to over-express SENP1 in prostate cancer cells with low metastatic potential (LNCaP). We showed that silencing of SENP1 promoted cellular apoptosis, and inhibited proliferation and migration of PC3M cells. Moreover, SENP1 silencing increased the SMAD4 expression at protein level, up-regulated E-cadherin and down-regulated Vimentin expression, indicating the inhibition of epithelial mesenchymal transition (EMT). Furthermore, SMAD4 interference abolished SENP1-mediated up-regulation of E-cadherin, suggesting that SENP1 regulated E-cadherin expression via SMAD4. SENP1 over-expression in LNCaP cells reduced SMAD4 protein, and promoted EMT via decreasing E-cadherin and increasing Vimentin. Moreover, down-regulation of SMAD4 and E-cadherin were blocked, after transfection with two SUMOylation sites mutated SMAD4, suggesting that SENP1 might reduce SMAD4 levels to regulate E-cadherin expression via deSUMOylation of SMAD4. In conclusion, SENP1 deSUMOylated SMAD4 to promote EMT via up-regulating E-cadherin in prostate cancer cells. Therefore, SENP1 is a potential target for treatment of advanced prostate cancer.

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Section: Discussionmentioning

confidence: 99%

SUMO-Specific Cysteine Protease 1 Promotes Epithelial Mesenchymal Transition of Prostate Cancer Cells via Regulating SMAD4 deSUMOylation

Zhang¹,

Wang²,

Wang³

et al. 2017

IJMS

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“…Although androgen ablation therapy is initially effective for the majority of men with metastatic prostate cancer, resistance to such treatment invariably develops through mechanisms that remain incompletely understood [23,24]. Most CRPCs express AR and are dependent on AR for growth and survival, through mechanisms reported to involve constitutive activation of AR [25,26].…”

Section: Discussionmentioning

confidence: 99%

HEXIM1 plays a critical role in the inhibition of the androgen receptor by anti-androgens

Yeh

Song

Wittmann

et al. 2014

Biochemical Journal

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We show that HEXIM1 (hexamethylene bis-acetamide inducible 1) functions as an AR (androgen receptor) co-repressor as it physically interacts with the AR and is required for the ability of anti-androgens to inhibit androgen-induced target gene expression and cell proliferation. Oncomine™ database and IHC (immunohistochemistry) analyses of human prostate tissues revealed that expression of HEXIM1 mRNA and protein are down-regulated during the development and progression of prostate cancer. Enforced down-regulation of HEXIM1 in parental hormone-dependent LNCaP cells results in resistance to the inhibitory action of anti-androgens. Conversely, ectopic expression of HEXIM1 in the CRPC (castration-resistant prostate cancer) cell line, C4-2, enhances their sensitivity to the repressive effects of the anti-androgen bicalutamide. Novel insight into the mechanistic basis for HEXIM1 inhibition of AR activity is provided by the present studies showing that HEXIM1 induces expression of the histone demethylase KDM5B (lysine-specific demethylase 5B) and inhibits histone methylation, resulting in the inhibition of FOXA1 (forkhead box A1) licensing activity. This is a new mechanism of action attributed to HEXIM1, and distinct from what has been reported so far to be involved in HEXIM1 regulation of other nuclear hormone receptors, including the oestrogen receptor.

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“…41 ADT severely reduces testosterone levels, which may impact cognitive function in subtle but meaningful ways for patients. 37 Because aromatase converts testosterone to estrogen, blocking testosterone lowers estrogen levels.…”

Section: Treatment-related Mechanismsmentioning

confidence: 99%

Proposed Mechanisms for Cancer- and Treatment-Related Cognitive Changes

Merriman¹,

Ah²,

Miaskowski³

et al. 2013

Seminars in Oncology Nursing

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Objectives To review the proposed mechanisms of cognitive changes associated with non-central nervous system cancers and cancer treatment. Data Sources Review and synthesis of data-based publications and review articles. Conclusion Proposed mechanisms include cytokine upregulation, hormonal changes, neurotransmitter dysregulation, attentional fatigue, genetic predisposition, and comorbid symptoms. Implications for Nursing Practice Oncology nurses need to understand the multiple mechanisms that may contribute to the development of cancer- and treatment-related cognitive changes so that they can identify patients at high risk and can help patients understand why these changes occur.

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Androgen Deprivation Therapy as Primary Treatment for Prostate Cancer

Cited by 33 publications

References 30 publications

SUMO-Specific Cysteine Protease 1 Promotes Epithelial Mesenchymal Transition of Prostate Cancer Cells via Regulating SMAD4 deSUMOylation

SUMO-Specific Cysteine Protease 1 Promotes Epithelial Mesenchymal Transition of Prostate Cancer Cells via Regulating SMAD4 deSUMOylation

HEXIM1 plays a critical role in the inhibition of the androgen receptor by anti-androgens

Proposed Mechanisms for Cancer- and Treatment-Related Cognitive Changes

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