Eintrag weiter verarbeiten
Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling
Gespeichert in:
| Zeitschriftentitel: | Molecular Cancer Therapeutics |
|---|---|
| Personen und Körperschaften: | , , , , , , |
| In: | Molecular Cancer Therapeutics, 17, 2018, 6, S. 1303-1314 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Inoue, Satoshi Ide, Hiroki Mizushima, Taichi Jiang, Guiyang Netto, George J. Gotoh, Momokazu Miyamoto, Hiroshi Inoue, Satoshi Ide, Hiroki Mizushima, Taichi Jiang, Guiyang Netto, George J. Gotoh, Momokazu Miyamoto, Hiroshi |
|---|---|
| author |
Inoue, Satoshi Ide, Hiroki Mizushima, Taichi Jiang, Guiyang Netto, George J. Gotoh, Momokazu Miyamoto, Hiroshi |
| spellingShingle |
Inoue, Satoshi Ide, Hiroki Mizushima, Taichi Jiang, Guiyang Netto, George J. Gotoh, Momokazu Miyamoto, Hiroshi Molecular Cancer Therapeutics Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling Cancer Research Oncology |
| author_sort |
inoue, satoshi |
| spelling |
Inoue, Satoshi Ide, Hiroki Mizushima, Taichi Jiang, Guiyang Netto, George J. Gotoh, Momokazu Miyamoto, Hiroshi 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-17-0786 <jats:title>Abstract</jats:title> <jats:p>We investigated the role of NF-κB in the development and progression of urothelial cancer as well as cross-talk between NF-κB and androgen receptor (AR) signals in urothelial cells. Immunohistochemistry in surgical specimens showed that the expression levels of NF-κB/p65 (P = 0.015)/phospho-NF-κB/p65 (P &lt; 0.001) were significantly elevated in bladder tumors, compared with those in nonneoplastic urothelial tissues. The rates of phospho-NF-κB/p65 positivity were also significantly higher in high-grade (P = 0.015)/muscle-invasive (P = 0.033) tumors than in lower grade/non–muscle-invasive tumors. Additionally, patients with phospho-NF-κB/p65-positive muscle-invasive bladder cancer had significantly higher risks of disease progression (P &lt; 0.001) and cancer-specific mortality (P = 0.002). In immortalized human normal urothelial SVHUC cells stably expressing AR, NF-κB activators and inhibitors accelerated and prevented, respectively, their neoplastic transformation induced by a chemical carcinogen 3-methylcholanthrene. Bladder tumors were identified in 56% (mock), 89% (betulinic acid), and 22% (parthenolide) of N-butyl-N-(4-hydroxybutyl)nitrosamine-treated male C57BL/6 mice at 22 weeks of age. NF-κB activators and inhibitors also significantly induced and reduced, respectively, cell proliferation/migration/invasion of AR-positive bladder cancer lines, but not AR-knockdown or AR-negative lines, and their growth in xenograft-bearing mice. In both nonneoplastic and neoplastic urothelial cells, NF-κB activators/inhibitors upregulated/downregulated, respectively, AR expression, whereas AR overexpression was associated with increases in the expression levels of NF-κB/p65 and phospho-NF-κB/p65. Thus, NF-κB appeared to be activated in bladder cancer, which was associated with tumor progression. NF-κB activators/inhibitors were also found to modulate tumorigenesis and tumor outgrowth in AR-activated urothelial cells. Accordingly, NF-κB inhibition, together with AR inactivation, has the potential of being an effective chemopreventive and/or therapeutic approach for urothelial carcinoma. Mol Cancer Ther; 17(6); 1303–14. ©2018 AACR.</jats:p> Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling Molecular Cancer Therapeutics |
| doi_str_mv |
10.1158/1535-7163.mct-17-0786 |
| facet_avail |
Online Free |
| finc_class_facet |
Medizin |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE1OC8xNTM1LTcxNjMubWN0LTE3LTA3ODY |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE1OC8xNTM1LTcxNjMubWN0LTE3LTA3ODY |
| institution |
DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 |
| imprint |
American Association for Cancer Research (AACR), 2018 |
| imprint_str_mv |
American Association for Cancer Research (AACR), 2018 |
| issn |
1535-7163 1538-8514 |
| issn_str_mv |
1535-7163 1538-8514 |
| language |
English |
| mega_collection |
American Association for Cancer Research (AACR) (CrossRef) |
| match_str |
inoue2018nuclearfactorkbpromotesurothelialtumorigenesisandcancerprogressionviacooperationwithandrogenreceptorsignaling |
| publishDateSort |
2018 |
| publisher |
American Association for Cancer Research (AACR) |
| recordtype |
ai |
| record_format |
ai |
| series |
Molecular Cancer Therapeutics |
| source_id |
49 |
| title |
Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling |
| title_unstemmed |
Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling |
| title_full |
Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling |
| title_fullStr |
Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling |
| title_full_unstemmed |
Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling |
| title_short |
Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling |
| title_sort |
nuclear factor-κb promotes urothelial tumorigenesis and cancer progression via cooperation with androgen receptor signaling |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/1535-7163.mct-17-0786 |
| publishDate |
2018 |
| physical |
1303-1314 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>We investigated the role of NF-κB in the development and progression of urothelial cancer as well as cross-talk between NF-κB and androgen receptor (AR) signals in urothelial cells. Immunohistochemistry in surgical specimens showed that the expression levels of NF-κB/p65 (P = 0.015)/phospho-NF-κB/p65 (P &lt; 0.001) were significantly elevated in bladder tumors, compared with those in nonneoplastic urothelial tissues. The rates of phospho-NF-κB/p65 positivity were also significantly higher in high-grade (P = 0.015)/muscle-invasive (P = 0.033) tumors than in lower grade/non–muscle-invasive tumors. Additionally, patients with phospho-NF-κB/p65-positive muscle-invasive bladder cancer had significantly higher risks of disease progression (P &lt; 0.001) and cancer-specific mortality (P = 0.002). In immortalized human normal urothelial SVHUC cells stably expressing AR, NF-κB activators and inhibitors accelerated and prevented, respectively, their neoplastic transformation induced by a chemical carcinogen 3-methylcholanthrene. Bladder tumors were identified in 56% (mock), 89% (betulinic acid), and 22% (parthenolide) of N-butyl-N-(4-hydroxybutyl)nitrosamine-treated male C57BL/6 mice at 22 weeks of age. NF-κB activators and inhibitors also significantly induced and reduced, respectively, cell proliferation/migration/invasion of AR-positive bladder cancer lines, but not AR-knockdown or AR-negative lines, and their growth in xenograft-bearing mice. In both nonneoplastic and neoplastic urothelial cells, NF-κB activators/inhibitors upregulated/downregulated, respectively, AR expression, whereas AR overexpression was associated with increases in the expression levels of NF-κB/p65 and phospho-NF-κB/p65. Thus, NF-κB appeared to be activated in bladder cancer, which was associated with tumor progression. NF-κB activators/inhibitors were also found to modulate tumorigenesis and tumor outgrowth in AR-activated urothelial cells. Accordingly, NF-κB inhibition, together with AR inactivation, has the potential of being an effective chemopreventive and/or therapeutic approach for urothelial carcinoma. Mol Cancer Ther; 17(6); 1303–14. ©2018 AACR.</jats:p> |
| container_issue |
6 |
| container_start_page |
1303 |
| container_title |
Molecular Cancer Therapeutics |
| container_volume |
17 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792348160174063622 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T18:06:45.582Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Nuclear+Factor-%CE%BAB+Promotes+Urothelial+Tumorigenesis+and+Cancer+Progression+via+Cooperation+with+Androgen+Receptor+Signaling&rft.date=2018-06-01&genre=article&issn=1538-8514&volume=17&issue=6&spage=1303&epage=1314&pages=1303-1314&jtitle=Molecular+Cancer+Therapeutics&atitle=Nuclear+Factor-%CE%BAB+Promotes+Urothelial+Tumorigenesis+and+Cancer+Progression+via+Cooperation+with+Androgen+Receptor+Signaling&aulast=Miyamoto&aufirst=Hiroshi&rft_id=info%3Adoi%2F10.1158%2F1535-7163.mct-17-0786&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792348160174063622 |
| author | Inoue, Satoshi, Ide, Hiroki, Mizushima, Taichi, Jiang, Guiyang, Netto, George J., Gotoh, Momokazu, Miyamoto, Hiroshi |
| author_facet | Inoue, Satoshi, Ide, Hiroki, Mizushima, Taichi, Jiang, Guiyang, Netto, George J., Gotoh, Momokazu, Miyamoto, Hiroshi, Inoue, Satoshi, Ide, Hiroki, Mizushima, Taichi, Jiang, Guiyang, Netto, George J., Gotoh, Momokazu, Miyamoto, Hiroshi |
| author_sort | inoue, satoshi |
| container_issue | 6 |
| container_start_page | 1303 |
| container_title | Molecular Cancer Therapeutics |
| container_volume | 17 |
| description | <jats:title>Abstract</jats:title> <jats:p>We investigated the role of NF-κB in the development and progression of urothelial cancer as well as cross-talk between NF-κB and androgen receptor (AR) signals in urothelial cells. Immunohistochemistry in surgical specimens showed that the expression levels of NF-κB/p65 (P = 0.015)/phospho-NF-κB/p65 (P &lt; 0.001) were significantly elevated in bladder tumors, compared with those in nonneoplastic urothelial tissues. The rates of phospho-NF-κB/p65 positivity were also significantly higher in high-grade (P = 0.015)/muscle-invasive (P = 0.033) tumors than in lower grade/non–muscle-invasive tumors. Additionally, patients with phospho-NF-κB/p65-positive muscle-invasive bladder cancer had significantly higher risks of disease progression (P &lt; 0.001) and cancer-specific mortality (P = 0.002). In immortalized human normal urothelial SVHUC cells stably expressing AR, NF-κB activators and inhibitors accelerated and prevented, respectively, their neoplastic transformation induced by a chemical carcinogen 3-methylcholanthrene. Bladder tumors were identified in 56% (mock), 89% (betulinic acid), and 22% (parthenolide) of N-butyl-N-(4-hydroxybutyl)nitrosamine-treated male C57BL/6 mice at 22 weeks of age. NF-κB activators and inhibitors also significantly induced and reduced, respectively, cell proliferation/migration/invasion of AR-positive bladder cancer lines, but not AR-knockdown or AR-negative lines, and their growth in xenograft-bearing mice. In both nonneoplastic and neoplastic urothelial cells, NF-κB activators/inhibitors upregulated/downregulated, respectively, AR expression, whereas AR overexpression was associated with increases in the expression levels of NF-κB/p65 and phospho-NF-κB/p65. Thus, NF-κB appeared to be activated in bladder cancer, which was associated with tumor progression. NF-κB activators/inhibitors were also found to modulate tumorigenesis and tumor outgrowth in AR-activated urothelial cells. Accordingly, NF-κB inhibition, together with AR inactivation, has the potential of being an effective chemopreventive and/or therapeutic approach for urothelial carcinoma. Mol Cancer Ther; 17(6); 1303–14. ©2018 AACR.</jats:p> |
| doi_str_mv | 10.1158/1535-7163.mct-17-0786 |
| facet_avail | Online, Free |
| finc_class_facet | Medizin |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE1OC8xNTM1LTcxNjMubWN0LTE3LTA3ODY |
| imprint | American Association for Cancer Research (AACR), 2018 |
| imprint_str_mv | American Association for Cancer Research (AACR), 2018 |
| institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161 |
| issn | 1535-7163, 1538-8514 |
| issn_str_mv | 1535-7163, 1538-8514 |
| language | English |
| last_indexed | 2024-03-01T18:06:45.582Z |
| match_str | inoue2018nuclearfactorkbpromotesurothelialtumorigenesisandcancerprogressionviacooperationwithandrogenreceptorsignaling |
| mega_collection | American Association for Cancer Research (AACR) (CrossRef) |
| physical | 1303-1314 |
| publishDate | 2018 |
| publishDateSort | 2018 |
| publisher | American Association for Cancer Research (AACR) |
| record_format | ai |
| recordtype | ai |
| series | Molecular Cancer Therapeutics |
| source_id | 49 |
| spelling | Inoue, Satoshi Ide, Hiroki Mizushima, Taichi Jiang, Guiyang Netto, George J. Gotoh, Momokazu Miyamoto, Hiroshi 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-17-0786 <jats:title>Abstract</jats:title> <jats:p>We investigated the role of NF-κB in the development and progression of urothelial cancer as well as cross-talk between NF-κB and androgen receptor (AR) signals in urothelial cells. Immunohistochemistry in surgical specimens showed that the expression levels of NF-κB/p65 (P = 0.015)/phospho-NF-κB/p65 (P &lt; 0.001) were significantly elevated in bladder tumors, compared with those in nonneoplastic urothelial tissues. The rates of phospho-NF-κB/p65 positivity were also significantly higher in high-grade (P = 0.015)/muscle-invasive (P = 0.033) tumors than in lower grade/non–muscle-invasive tumors. Additionally, patients with phospho-NF-κB/p65-positive muscle-invasive bladder cancer had significantly higher risks of disease progression (P &lt; 0.001) and cancer-specific mortality (P = 0.002). In immortalized human normal urothelial SVHUC cells stably expressing AR, NF-κB activators and inhibitors accelerated and prevented, respectively, their neoplastic transformation induced by a chemical carcinogen 3-methylcholanthrene. Bladder tumors were identified in 56% (mock), 89% (betulinic acid), and 22% (parthenolide) of N-butyl-N-(4-hydroxybutyl)nitrosamine-treated male C57BL/6 mice at 22 weeks of age. NF-κB activators and inhibitors also significantly induced and reduced, respectively, cell proliferation/migration/invasion of AR-positive bladder cancer lines, but not AR-knockdown or AR-negative lines, and their growth in xenograft-bearing mice. In both nonneoplastic and neoplastic urothelial cells, NF-κB activators/inhibitors upregulated/downregulated, respectively, AR expression, whereas AR overexpression was associated with increases in the expression levels of NF-κB/p65 and phospho-NF-κB/p65. Thus, NF-κB appeared to be activated in bladder cancer, which was associated with tumor progression. NF-κB activators/inhibitors were also found to modulate tumorigenesis and tumor outgrowth in AR-activated urothelial cells. Accordingly, NF-κB inhibition, together with AR inactivation, has the potential of being an effective chemopreventive and/or therapeutic approach for urothelial carcinoma. Mol Cancer Ther; 17(6); 1303–14. ©2018 AACR.</jats:p> Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling Molecular Cancer Therapeutics |
| spellingShingle | Inoue, Satoshi, Ide, Hiroki, Mizushima, Taichi, Jiang, Guiyang, Netto, George J., Gotoh, Momokazu, Miyamoto, Hiroshi, Molecular Cancer Therapeutics, Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling, Cancer Research, Oncology |
| title | Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling |
| title_full | Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling |
| title_fullStr | Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling |
| title_full_unstemmed | Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling |
| title_short | Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling |
| title_sort | nuclear factor-κb promotes urothelial tumorigenesis and cancer progression via cooperation with androgen receptor signaling |
| title_unstemmed | Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/1535-7163.mct-17-0786 |