scholarly journals Dehydroepiandrosterone Administration or Gαq Overexpression Induces β-Catenin/T-Cell Factor Signaling and Growth via Increasing Association of Estrogen Receptor-β/Dishevelled2 in Androgen-Independent Prostate Cancer Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1428-1440 ◽  
Author(s):  
Xunxian Liu ◽  
Julia T. Arnold ◽  
Marc R. Blackman
Keyword(s):  
Prostate Cancer ◽  
Estrogen Receptor ◽  
T Cell ◽  
Cell Growth ◽  
Protein Expression ◽  
Cyclin D1 ◽  
D1 Protein ◽  
Nutritional Supplement ◽  
T Cell Factor ◽  
Androgen Independent

β-Catenin/T-cell factor signaling (β-CTS) plays multiple critical roles in carcinogenesis and is blocked by androgens in androgen receptor (AR)-responsive prostate cancer (PrCa) cells, primarily via AR sequestration of β-catenin from T-cell factor. Dehydroepiandrosterone (DHEA), often used as an over-the-counter nutritional supplement, is metabolized to androgens and estrogens in humans. The efficacy and safety of unregulated use of DHEA are unclear. We now report that DHEA induces β-CTS via increasing association of estrogen receptor (ER)-β with Dishevelled2 (Dvl2) in AR nonresponsive human PrCa DU145 cells, a line of androgen-independent PrCa (AiPC) cells. The induction is temporal, as assessed by measuring kinetics of the association of ERβ/Dvl2, protein expression of the β-CTS targeted genes, c-Myc and cyclin D1, and cell growth. However, in PC-3 cells, another human AiPC cell line, DHEA exerts no detectible effects, partly due to their lower expression of Gα-subunits and DHEA down-regulation of ERβ/Dvl2 association. When Gαq is overexpressed in PC-3 cells, β-CTS is constitutively induced, including increasing c-Myc and cyclin D1 protein expression. This effect involved increasing associations of Gαq/Dvl2 and ERβ/Dvl2 and promoted cell growth. These activities require ERβ in DU-145 and PC-3 cells because they are blocked by ICI 182–780 treatment inactivating ERβ, small interfering RNA administration depleting ERβ, or AR overexpression arresting ERβ. These data suggest that novel pathways activating β-CTS play roles in the progression of AiPC. Although DHEA may enhance PrCa cell growth via androgenic or estrogenic pathways, the effects of DHEA administration on clinical prostate function remain to be determined.

mTOR function in skeletal muscle hypertrophy: increased ribosomal RNA via cell cycle regulators

2005 ◽  
Vol 289 (6) ◽  
pp. C1457-C1465 ◽  
Author(s):  
Gustavo A. Nader ◽  
Thomas J. McLoughlin ◽  
Karyn A. Esser
Keyword(s):  
Cell Cycle ◽  
Protein Expression ◽  
Cyclin D1 ◽  
Ribosomal Rna ◽  
Molecular Mechanisms ◽  
D1 Protein ◽  
Rna Content ◽  
Cyclin D1 Protein ◽  
Rb Phosphorylation ◽  
Myotube Hypertrophy

The purpose of this study was to identify the potential downstream functions associated with mammalian target of rapamycin (mTOR) signaling during myotube hypertrophy. Terminally differentiated myotubes were serum stimulated for 3, 6, 12, 24, and 48 h. This treatment resulted in significant myotube hypertrophy (protein/DNA) and increased RNA content (RNA/DNA) with no changes in DNA content or indices of cell proliferation. During myotube hypertrophy, the increase in RNA content was accompanied by an increase in tumor suppressor protein retinoblastoma (Rb) phosphorylation and a corresponding increase in the availability of the ribosomal DNA transcription factor upstream binding factor (UBF). Serum stimulation also induced an increase in cyclin D1 protein expression in the differentiated myotubes with a concomitant increase in cyclin D1-dependent cyclin-dependent kinase (CDK)-4 activity toward Rb. The increases in myotube hypertrophy and RNA content were blocked by rapamycin treatment, which also prevented the increase in cyclin D1 protein expression, CDK-4 activity, Rb phosphorylation, and the increase in UBF availability. Our findings demonstrate that activation of mTOR is necessary for myotube hypertrophy and suggest that the role of mTOR is in part to modulate cyclin D1-dependent CDK-4 activity in the regulation of Rb and ribosomal RNA synthesis. On the basis of these results, we propose that common molecular mechanisms contribute to the regulation of myotube hypertrophy and growth during the G1 phase of the cell cycle.

scholarly journals HOXB13 Homeodomain Protein Suppresses the Growth of Prostate Cancer Cells by the Negative Regulation of T-Cell Factor 4

2004 ◽  
Vol 64 (9) ◽  
pp. 3046-3051 ◽  
Author(s):  
Chaeyong Jung ◽  
Ran-Sook Kim ◽  
Sang-Jin Lee ◽  
Chihuei Wang ◽  
Meei-Huey Jeng
Keyword(s):  
Prostate Cancer ◽  
T Cell ◽  
Cancer Cells ◽  
Negative Regulation ◽  
Homeodomain Protein ◽  
Prostate Cancer Cells ◽  
T Cell Factor

scholarly journals L-securinine inhibits cell growth and metastasis of human androgen-independent prostate cancer DU145 cells via regulating mitochondrial and AGTR1/MEK/ERK/STAT3/PAX2 apoptotic pathways

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Dongxu Zhang ◽  
Houxian Liu ◽  
Binbin Yang ◽  
Jiasheng Hu ◽  
Yue Cheng
Keyword(s):  
Prostate Cancer ◽  
Protein Expression ◽  
Annexin V ◽  
Inhibitory Effect ◽  
Apoptotic Pathway ◽  
Growth Inhibitory ◽  
Du145 Cells ◽  
Apoptotic Pathways ◽  
Induced Apoptosis ◽  
Androgen Independent

Abstract The present study aims to evaluate the anticancer effect of L-securinine on androgen-independent prostate cancer (AIPC) DU145 cells. L-securinine (2.5, 5, and 10 μM) treatment for 24, 48 and 72 h displayed strong growth inhibitory effect on DU145 cells in a concentration and time-dependent fashion but has less toxicity toward normal androgen-dependent LNCaP cells. Hoechst 332582 staining of DU145 cells and Annexin V-FITC/ PI dual-labeling followed by flow cytometry assay identified that this growth inhibition by L-securinine would be due to the induction of apoptosis. Moreover Transwell assay revealed that L-securinine significantly inhibited the cell migration/invasion ability of DU145 cells. Furthermore, results of western blotting showed that the involvement of mitochondrial apoptotic pathway in the L-securinine-induced apoptosis of DU145 cell, as evidenced by an increase in the protein expression of Bax, cleaved caspase-9, cleaved caspase-3, cytosolic cytochrome c, and cleaved PARP, together with a unchanged cleaved caspase-8 and decreased Bcl-2 protein expression. Also, L-securinine-induced antimetastatic activity in DU145 cells was associated with decreased protein expression of MMP-2 and MMP-9 and concurrent reduction of VEGF. In addition, further studies revealed that L-securinine may inhibit the protein expression of AGTR1, p-MEK1/2, p-ERK1/2, p-STAT3, PAX2, and p-PAX2, while the expression of ERK1/2, MEK1/2, and STAT3 protein retains intact. These findings suggest that L-securinine may be a promising chemopreventive agent against AIPC.

scholarly journals Evidence that androgen-independent stromal growth factor signals promote androgen-insensitive prostate cancer cell growth in vivo

2009 ◽  
Vol 16 (2) ◽  
pp. 415-428 ◽  
Author(s):  
Kenichiro Ishii ◽  
Tetsuya Imamura ◽  
Kazuhiro Iguchi ◽  
Shigeki Arase ◽  
Yuko Yoshio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Cell Growth ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Receptor Expression ◽  
Urogenital Sinus ◽  
Cancer Cell Growth ◽  
Androgen Ablation ◽  
Androgen Independent

Activation of tumor–stromal interactions is considered to play a critical role in the promotion of tumorigenesis. To discover new therapeutic targets for hormone-refractory prostate tumor growth under androgen ablation therapy, androgen-sensitive LNCaP cells and the derived sublines, E9 (androgen-low-sensitive), and AIDL (androgen-insensitive), were recombined with androgen-dependent embryonic rat urogenital sinus mesenchyme (UGM). Tumors of E9+UGM and AIDL+UGM were approximately three times as large as those of LNCaP+UGM. Tumors grown in castrated hosts exhibited reduced growth as compared with those in intact hosts. However, in castrated hosts, E9+UGM and AIDL+UGM tumors were still approximately twice as large as those of LNCaP+UGM. Cell proliferation in tumors of E9+UGM and AIDL+UGM grown in castrated host, was significantly higher than that in tumors of LNCaP+UGM. In vitro, expression of fibroblast growth factor (FGF)-2 and IGF-I, but not FGF-7 mRNA, was significantly reduced in UGM under androgen starvation. In cell culture, E9 cells were responsive to FGF-2 and FGF-7 stimulation, while AIDL responded to FGF-7 and IGF-1. Expression of FGFR1 and FGFR2 was considerably higher in E9 than those in LNCaP, similarly expression of FGFR2 and IGF-IR were elevated in AIDL. These data suggest that activation of prostate cancer cell growth through growth factor receptor expression may result in the activity of otherwise androgen-independent stromal growth factor signals such as FGF-7 under conditions of androgen ablation.

Phosphoproteome analysis demonstrates the potential role of THRAP3 phosphorylation in androgen-independent prostate cancer cell growth

PROTEOMICS ◽  
2016 ◽  
Vol 16 (7) ◽  
pp. 1069-1078 ◽  
Author(s):  
Yoko Ino ◽  
Noriaki Arakawa ◽  
Hitoshi Ishiguro ◽  
Hiroji Uemura ◽  
Yoshinobu Kubota ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Potential Role ◽  
Prostate Cancer Cell ◽  
Cancer Cell Growth ◽  
Androgen Independent
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