Castration resistance of prostate cancer cells caused by castration-induced oxidative stress through Twist1 and androgen receptor overexpression

Shiota, Masaki; Yokomizo, Akira; Tada, Yasuhiro; Inokuchi, Junichi; Kashiwagi, Eiji; Masubuchi, Daisuke; Eto, Masatoshi; Uchiumi, Takeshi; Naito, Seiji

doi:10.1038/onc.2009.322

Cited by 115 publications

(153 citation statements)

References 41 publications

Supporting

Mentioning

146

Contrasting

Order By: Relevance

“…Conversely, we have reported that Twist1 regulated AR expression in LNCaP and 22Rv1 cells (Shiota et al 2010), suggesting that the contribution of Twist1 to castration resistance through augmented AR signaling. Therefore, we speculated that AR expression might be induced by TGF-b stimulation via the Twist1 transcription factor.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown that Twist1 promoted prostate cancer growth through the regulation of AR expression (Shiota et al 2010(Shiota et al , 2014. In addition, Twist1 was up-regulated following androgen ablation in human prostate cancer tissues (Shiota et al 2012b), suggesting that Twist1 confers castration resistance to androgen-dependent prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Whole-cell extracts were prepared as described previously (Shiota et al 2010(Shiota et al , 2011a(Shiota et al , 2012b. Briefly, the concentration of the prepared protein extracts was quantified using a Protein Assay (Bio-Rad Laboratories) based on the Bradford method.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…RNA isolation and RT were performed as described previously (Shiota et al 2010(Shiota et al , 2011a(Shiota et al , 2012b. Quantitative real-time PCR was performed using TaqMan Gene Expression Assays for Twist1 (Hs00361186_m1), fulllength AR (Hs00907244_m1), AR V7 (custom-made; primer and probe sequences were described previously in Liu et al (2014) …”

Section: Rna Isolation Rt and Quantitative Real-time Pcrmentioning

confidence: 99%

See 3 more Smart Citations

Crosstalk between epithelial-mesenchymal transition and castration resistance mediated by Twist1/AR signaling in prostate cancer

Shiota¹,

Itsumi²,

Takeuchi³

et al. 2015

Endocrine-Related Cancer

View full text Add to dashboard Cite

Although invasive and metastatic progression via the epithelial-mesenchymal transition (EMT) and acquisition of resistance to castration are both critical steps in prostate cancer, the molecular mechanism of this interaction remains unclear. In this study, we aimed to elucidate the interaction of signaling between castration resistance and EMT, and to apply this information to the development of a novel therapeutic concept using transforming growth factor-b (TGF-b) inhibitor SB525334 combined with androgen-deprivation therapy against prostate cancer using an in vivo model. This study revealed that an EMT inducer (TGF-b) induced full-length androgen receptor (AR) and AR variant expression. In addition, a highly invasive clone showed augmented full-length AR and AR variant expression as well as acquisition of castration resistance. Conversely, full-length AR and AR as well as Twist1 and mesenchymal molecules variant expression were up-regulated in castration-resistant LNCaP xenograft. Finally, TGF-b inhibitor suppressed Twist1 and AR expression as well as prostate cancer growth combined with castration. Taken together, these results demonstrate that Twist1/AR signaling was augmented in castration resistant as well as mesenchymal-phenotype prostate cancer, indicating the molecular mechanism of mutual and functional crosstalk between EMT and castration resistance, which may play a crucial role in prostate carcinogenesis and progression.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

Section: Rna Isolation Rt and Quantitative Real-time Pcrmentioning

confidence: 99%

See 2 more Smart Citations

Crosstalk between epithelial-mesenchymal transition and castration resistance mediated by Twist1/AR signaling in prostate cancer

Shiota¹,

Itsumi²,

Takeuchi³

et al. 2015

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…Passage 10-40 LNCaP cells were used in experiments. A castration-resistant derivative of LNCaP cells, LNCaP-CxR cells (referred to as CxR cells), was established and maintained as described previously (Shiota et al 2010b). The cell lines were maintained at 37 8C with 5% CO 2 .…”

Section: Cell Culturementioning

confidence: 99%

Human heterochromatin protein 1 isoforms regulate androgen receptor signaling in prostate cancer

Itsumi¹,

Shiota²,

Yokomizo³

et al. 2013

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Androgen receptor (AR) signaling is critical for the tumorigenesis and development of prostate cancer, as well as the progression to castration-resistant prostate cancer. We previously showed that the heterochromatin protein 1 (HP1) b isoform plays a critical role in transactivation of AR signaling as an AR coactivator that promotes prostate cancer cell proliferation. However, the roles of other HP1 isoforms, HP1a and HP1g, in AR expression and prostate cancer remain unclear. Here, we found that knockdown of HP1g, but not HP1a, reduced AR expression and cell proliferation by inducing cell cycle arrest at G1 phase in LNCaP cells. Conversely, overexpression of full-length HP1a and its C-terminal deletion mutant increased AR expression and cell growth, whereas overexpression of HP1g had no effect. Similarly, HP1a overexpression promoted 22Rv1 cell growth, whereas HP1g knockdown reduced the proliferation of CxR cells, a castration-resistant LNCaP derivative. Taken together, HP1 isoforms distinctly augment AR signaling and cell growth in prostate cancer. Therefore, silencing of HP1b and HP1g may be a promising therapeutic strategy for treatment of prostate cancer.

show abstract

Catalase Inhibitors with Dual Pro‐Oxidant Effect as New Therapeutic Agents in Castration‐Resistant Prostate Cancer

Chen

Liang

Liu

et al. 2020

Advanced Therapeutics

View full text Add to dashboard Cite

Almost all patients with advanced prostate cancer (PCa) will eventually progress to incurable castration-resistant PCa (CRPC) if endocrine therapy fails. Therefore, identifying potential cellular targets is critical for the development of novel and effective treatments for CRPC. Based on the investigation of the molecular mechanism of ATN-224, an anticancer drug in clinical trials, in CRPC DU145 cells, the antioxidant enzyme catalase (CAT) has been recognized as an actionable CRPC therapeutic target, and the modulation of intracellular redox state through CAT inhibition has great potential for CRPC treatment. After systematic design and synthesis, the benzaldehyde thiosemicarbazone derivative BT-1 is shown to be effective CAT inhibitor in DU145 cells. This inhibition induces the significant increase of both superoxides (O 2 •−) and H 2 O 2 levels in DU145 cells. Finally, the dual pro-oxidant effect of BT-1 is demonstrated to lead to apoptosis as well as cell-cycle arrest in DU145 cells, effectively reducing CRPC tumors.

show abstract

Castration resistance of prostate cancer cells caused by castration-induced oxidative stress through Twist1 and androgen receptor overexpression

Cited by 115 publications

References 41 publications

Crosstalk between epithelial-mesenchymal transition and castration resistance mediated by Twist1/AR signaling in prostate cancer

Crosstalk between epithelial-mesenchymal transition and castration resistance mediated by Twist1/AR signaling in prostate cancer

Human heterochromatin protein 1 isoforms regulate androgen receptor signaling in prostate cancer

Catalase Inhibitors with Dual Pro‐Oxidant Effect as New Therapeutic Agents in Castration‐Resistant Prostate Cancer

Contact Info

Product

Resources

About