Androgen-mediated Control of the Cyclin D1-RB Axis: Implications for Prostate Cancer

Bone metastasis is a significant cause of morbidity and mortality in patients with prostate cancer (PCa). This study is aimed at illustrating the mechanism of sweroside-mediated regulation in bone metastasis in PCa cells. Owing to the limitations of antitumor drugs in terms of their physical and chemical properties, making them into nanomaterials can effectively improve drug stability and bioavailability. Apoptosis was assessed with flow cytometry using the annexin V/propidium iodide binding assay; proteins, including p53, P21, Bcl-2, and Bax; and induction of intracellular reactive oxygen species (ROS). Using colony formation assay, sphere formation assay, and the expression changes in CD133 and CD44, stem cell characteristics were assessed. Epithelial–mesenchymal transition (EMT) activity was accessed by levels of the expression changes of EMT-related markers, vimentin and E-cadherin. Wnt/β-catenin signaling pathway was examined to detect the levels of the expression changes of snail and β-catenin. PC-3 cells were treated with lithium chloride (LiCl), which is an agonist of Wnt/β-catenin signaling, and the levels of CD133, CD44, vimentin, E-cadherin, snail, and β-catenin were detected. T-cell factor/lymphocyte enhancer factor (TCF/LEF) activity in cells overexpressing β-catenin was used to detect the effects on β-catenin transcription, and the expression of c-myc, Cyclin D1, Survivin, and MMP-7 were used to detect Wnt downstream target genes. Our results suggest that sweroside induces apoptosis and intracellular ROS; upregulates apoptotic proteins; and suppresses proliferation, invasion, and migration, preventing stem cell characteristics, including sphere formation, colony formation, and CD133 and CD44 expressions. Furthermore, sweroside nanoparticles exerts inhibitory effects on β-catenin transcription by suppressing TTCF/LEF activity in cells overexpressing β-catenin and downregulation of the expression of Wnt downstream target genes, including c-myc, Cyclin D1, Survivin, and MMP-7. The potential therapeutic effect of sweroside nanoparticles on bone metastatis of PCa was suggested, by these findings.

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Impact of cyclin D1 and DJ-1 on diagnosis, clinico-pathological features and outcome in prostate cancer and benign prostatic hyperplasia

Forum of Clinical Oncology ◽

10.2478/fco-2019-0005 ◽

2020 ◽

Vol 10 (2) ◽

pp. 15-25

Author(s):

Amrallah A. Mohammed ◽

Hanna M. Ibrahim ◽

Hanna A. Atwa ◽

Ayman Elshentenawy ◽

Amira Elwan

Keyword(s):

Prostate Cancer ◽

Benign Prostatic Hyperplasia ◽

Cyclin D1 ◽

Tumor Stage ◽

Prostatic Hyperplasia ◽

Common Finding ◽

Tissue Sampling ◽

Benign Lesions ◽

Significant Difference

AbstractBackgroundDisturbance in cell cycle regulatory genes is a common finding among many types of cancers. The aim of this study is to evaluate the role of cyclin D1 and DJ-1 in benign prostatic hyperplasia (BPH) and prostate cancer (PC).MethodThe current study enclosed 40 patients diagnosed with PC and 40 cases of BPH. The expression level of cyclin D1 and DJ-1 were evaluated by immunohistochemistry (IHC). Cyclin D1 scored depending on the percentage of stained nuclear tumor cells. While scoring of DJ-1 was based on intensity. The results were correlated with clinicopathological features and outcome.ResultsIn the PC group, cyclin D1 was detected in 95% and overexpressed in 42.5%, DJ-1 was positively stained in 85% and overexpressed in 47.5%. Meanwhile, in the BPH group, cyclin D1 was not detected and DJ-1 stained in only 2.5%. There was a statistically significant difference in Gleason score (GS), tumor stage, size, and treatment failure (p =< 0.001). In the terms of PC diagnosis prediction, although cyclin D1 was more specific (100%), DJ-1 is more sensitive than cyclin D1 (80%, 70%, respectively) (p = 0.000).ConclusionsCyclin D1 and DJ-1 may emerge as a promising way for diagnosis of PC in certain circumstances, as the presence of insufficient tissue sampling, small foci of carcinoma or benign lesions mimic PC. This is in addition to the known role of cyclin D1 and DJ-1 in PC prognosis.

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Correction: Cyclin D1 silencing suppresses tumorigenicity, impairs DNA double strand break repair and thus radiosensitizes androgen-independent prostate cancer cells to DNA damage

Oncotarget ◽

10.18632/oncotarget.12267 ◽

2016 ◽

Vol 7 (39) ◽

pp. 64526-64526 ◽

Cited By ~ 7

Author(s):

Francesco Marampon ◽

Giovanni Luca Gravina ◽

Xiaoming Ju ◽

Antonella Vetuschi ◽

Roberta Sferra ◽

...

Keyword(s):

Prostate Cancer ◽

Dna Damage ◽

Cyclin D1 ◽

Cancer Cells ◽

Strand Break ◽

Double Strand Break ◽

Double Strand Break Repair ◽

Prostate Cancer Cells ◽

Dna Double Strand Break ◽

Androgen Independent

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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 ◽

10.1210/en.2009-0885 ◽

2010 ◽

Vol 151 (4) ◽

pp. 1428-1440 ◽

Cited By ~ 11

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.

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