Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells

Autores
Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; Starbuck, Michael W.; Diao, Lixia; Wang, Jing; Efstathiou, Eleni; Vazquez, Elba Susana; Troncoso, Silvana Patricia; Maity, Sankar N.; Navone, Nora
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Purpose: To study Wnt/β-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the β-catenin-androgen receptor (AR) interaction. Experimental Design: We carried out β-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of β-catenin-mediated transcription), and sequenced the β-catenin gene inMDA prostate cancer 118a, MDA prostate cancer 118b, MDA prostate cancer 2b, and PC-3 prostate cancer cells. We knocked down β-catenin in AR-negative MDA prostate cancer 118b cells and carried out comparative gene-array analysis. We also immunohistochemically analyzed β-catenin and AR in 27 bone metastases of human CRPCs. Results: β-Catenin nuclear accumulation and TOP-flash reporter activity were high in MDA prostate cancer 118b but not in MDA prostate cancer 2b or PC-3 cells. MDA prostate cancer 118a and MDA prostate cancer 118b cells carry a mutated β-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA prostate cancer 118b cells with downregulated β-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant β-catenin. Finally, we found nuclear localization of β-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P=0.056, Fisher's exact test), suggesting that reduced AR expression enables Wnt/β-catenin signaling. Conclusion: We identified a previously unknown downstream target of β-catenin, HAS2, in prostate cancer, and found that high β-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone metastatic prostate cancer. These findings may guide physicians in managing these patients.
Fil: Wan, Xinhai. University of Texas; Estados Unidos
Fil: Liu, Jie. University of Texas; Estados Unidos
Fil: Lu, Jing-Fang. University of Texas; Estados Unidos
Fil: Tzelepi, Vassiliki. University of Texas; Estados Unidos
Fil: Yang, Jun. University of Texas; Estados Unidos
Fil: Starbuck, Michael W.. University of Texas; Estados Unidos
Fil: Diao, Lixia. University of Texas; Estados Unidos
Fil: Wang, Jing. University of Texas; Estados Unidos
Fil: Efstathiou, Eleni. University of Texas; Estados Unidos
Fil: Vazquez, Elba Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Troncoso, Silvana Patricia. University of Texas; Estados Unidos
Fil: Maity, Sankar N.. University of Texas; Estados Unidos
Fil: Navone, Nora. University of Texas; Estados Unidos
Materia
PROSTATE CANCER
BONE METASTASIS
B-CATENIN
ANDROGEN RECEPTOR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/100114
Acceder
id CONICETDig_70ac1fc57474b32641bef76bc8083397
oai_identifier_str oai:ri.conicet.gov.ar:11336/100114
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Activation of β-catenin signaling in androgen receptor-negative prostate cancer cellsWan, XinhaiLiu, JieLu, Jing-FangTzelepi, VassilikiYang, JunStarbuck, Michael W.Diao, LixiaWang, JingEfstathiou, EleniVazquez, Elba SusanaTroncoso, Silvana PatriciaMaity, Sankar N.Navone, NoraPROSTATE CANCERBONE METASTASISB-CATENINANDROGEN RECEPTORhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Purpose: To study Wnt/β-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the β-catenin-androgen receptor (AR) interaction. Experimental Design: We carried out β-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of β-catenin-mediated transcription), and sequenced the β-catenin gene inMDA prostate cancer 118a, MDA prostate cancer 118b, MDA prostate cancer 2b, and PC-3 prostate cancer cells. We knocked down β-catenin in AR-negative MDA prostate cancer 118b cells and carried out comparative gene-array analysis. We also immunohistochemically analyzed β-catenin and AR in 27 bone metastases of human CRPCs. Results: β-Catenin nuclear accumulation and TOP-flash reporter activity were high in MDA prostate cancer 118b but not in MDA prostate cancer 2b or PC-3 cells. MDA prostate cancer 118a and MDA prostate cancer 118b cells carry a mutated β-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA prostate cancer 118b cells with downregulated β-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant β-catenin. Finally, we found nuclear localization of β-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P=0.056, Fisher's exact test), suggesting that reduced AR expression enables Wnt/β-catenin signaling. Conclusion: We identified a previously unknown downstream target of β-catenin, HAS2, in prostate cancer, and found that high β-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone metastatic prostate cancer. These findings may guide physicians in managing these patients.Fil: Wan, Xinhai. University of Texas; Estados UnidosFil: Liu, Jie. University of Texas; Estados UnidosFil: Lu, Jing-Fang. University of Texas; Estados UnidosFil: Tzelepi, Vassiliki. University of Texas; Estados UnidosFil: Yang, Jun. University of Texas; Estados UnidosFil: Starbuck, Michael W.. University of Texas; Estados UnidosFil: Diao, Lixia. University of Texas; Estados UnidosFil: Wang, Jing. University of Texas; Estados UnidosFil: Efstathiou, Eleni. University of Texas; Estados UnidosFil: Vazquez, Elba Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Troncoso, Silvana Patricia. University of Texas; Estados UnidosFil: Maity, Sankar N.. University of Texas; Estados UnidosFil: Navone, Nora. University of Texas; Estados UnidosAmerican Association for Cancer Research2012-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/100114Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; et al.; Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells; American Association for Cancer Research; Clinical Cancer Research; 18; 3; 2-2012; 726-7361078-0432CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://clincancerres.aacrjournals.org/content/18/3/726.longinfo:eu-repo/semantics/altIdentifier/doi/10.1158/1078-0432.CCR-11-2521info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:07:52Zoai:ri.conicet.gov.ar:11336/100114instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:07:53.001CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells
title Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells
spellingShingle Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells
Wan, Xinhai
PROSTATE CANCER
BONE METASTASIS
B-CATENIN
ANDROGEN RECEPTOR
title_short Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells
title_full Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells
title_fullStr Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells
title_full_unstemmed Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells
title_sort Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells
dc.creator.none.fl_str_mv Wan, Xinhai
Liu, Jie
Lu, Jing-Fang
Tzelepi, Vassiliki
Yang, Jun
Starbuck, Michael W.
Diao, Lixia
Wang, Jing
Efstathiou, Eleni
Vazquez, Elba Susana
Troncoso, Silvana Patricia
Maity, Sankar N.
Navone, Nora
author Wan, Xinhai
author_facet Wan, Xinhai
Liu, Jie
Lu, Jing-Fang
Tzelepi, Vassiliki
Yang, Jun
Starbuck, Michael W.
Diao, Lixia
Wang, Jing
Efstathiou, Eleni
Vazquez, Elba Susana
Troncoso, Silvana Patricia
Maity, Sankar N.
Navone, Nora
author_role author
author2 Liu, Jie
Lu, Jing-Fang
Tzelepi, Vassiliki
Yang, Jun
Starbuck, Michael W.
Diao, Lixia
Wang, Jing
Efstathiou, Eleni
Vazquez, Elba Susana
Troncoso, Silvana Patricia
Maity, Sankar N.
Navone, Nora
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PROSTATE CANCER
BONE METASTASIS
B-CATENIN
ANDROGEN RECEPTOR
topic PROSTATE CANCER
BONE METASTASIS
B-CATENIN
ANDROGEN RECEPTOR
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Purpose: To study Wnt/β-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the β-catenin-androgen receptor (AR) interaction. Experimental Design: We carried out β-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of β-catenin-mediated transcription), and sequenced the β-catenin gene inMDA prostate cancer 118a, MDA prostate cancer 118b, MDA prostate cancer 2b, and PC-3 prostate cancer cells. We knocked down β-catenin in AR-negative MDA prostate cancer 118b cells and carried out comparative gene-array analysis. We also immunohistochemically analyzed β-catenin and AR in 27 bone metastases of human CRPCs. Results: β-Catenin nuclear accumulation and TOP-flash reporter activity were high in MDA prostate cancer 118b but not in MDA prostate cancer 2b or PC-3 cells. MDA prostate cancer 118a and MDA prostate cancer 118b cells carry a mutated β-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA prostate cancer 118b cells with downregulated β-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant β-catenin. Finally, we found nuclear localization of β-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P=0.056, Fisher's exact test), suggesting that reduced AR expression enables Wnt/β-catenin signaling. Conclusion: We identified a previously unknown downstream target of β-catenin, HAS2, in prostate cancer, and found that high β-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone metastatic prostate cancer. These findings may guide physicians in managing these patients.
Fil: Wan, Xinhai. University of Texas; Estados Unidos
Fil: Liu, Jie. University of Texas; Estados Unidos
Fil: Lu, Jing-Fang. University of Texas; Estados Unidos
Fil: Tzelepi, Vassiliki. University of Texas; Estados Unidos
Fil: Yang, Jun. University of Texas; Estados Unidos
Fil: Starbuck, Michael W.. University of Texas; Estados Unidos
Fil: Diao, Lixia. University of Texas; Estados Unidos
Fil: Wang, Jing. University of Texas; Estados Unidos
Fil: Efstathiou, Eleni. University of Texas; Estados Unidos
Fil: Vazquez, Elba Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Troncoso, Silvana Patricia. University of Texas; Estados Unidos
Fil: Maity, Sankar N.. University of Texas; Estados Unidos
Fil: Navone, Nora. University of Texas; Estados Unidos
description Purpose: To study Wnt/β-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the β-catenin-androgen receptor (AR) interaction. Experimental Design: We carried out β-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of β-catenin-mediated transcription), and sequenced the β-catenin gene inMDA prostate cancer 118a, MDA prostate cancer 118b, MDA prostate cancer 2b, and PC-3 prostate cancer cells. We knocked down β-catenin in AR-negative MDA prostate cancer 118b cells and carried out comparative gene-array analysis. We also immunohistochemically analyzed β-catenin and AR in 27 bone metastases of human CRPCs. Results: β-Catenin nuclear accumulation and TOP-flash reporter activity were high in MDA prostate cancer 118b but not in MDA prostate cancer 2b or PC-3 cells. MDA prostate cancer 118a and MDA prostate cancer 118b cells carry a mutated β-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA prostate cancer 118b cells with downregulated β-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant β-catenin. Finally, we found nuclear localization of β-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P=0.056, Fisher's exact test), suggesting that reduced AR expression enables Wnt/β-catenin signaling. Conclusion: We identified a previously unknown downstream target of β-catenin, HAS2, in prostate cancer, and found that high β-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone metastatic prostate cancer. These findings may guide physicians in managing these patients.
publishDate 2012
dc.date.none.fl_str_mv 2012-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/100114
Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; et al.; Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells; American Association for Cancer Research; Clinical Cancer Research; 18; 3; 2-2012; 726-736
1078-0432
CONICET Digital
CONICET
url http://hdl.handle.net/11336/100114
identifier_str_mv Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; et al.; Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells; American Association for Cancer Research; Clinical Cancer Research; 18; 3; 2-2012; 726-736
1078-0432
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://clincancerres.aacrjournals.org/content/18/3/726.long
info:eu-repo/semantics/altIdentifier/doi/10.1158/1078-0432.CCR-11-2521
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association for Cancer Research
publisher.none.fl_str_mv American Association for Cancer Research
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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