CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss.

Aromatase inhibitors (AIs) used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer cause diverse musculoskeletal side effects that include bone loss and its associated fracture. About half of the 391 patients treated with AIs in the Barcelona-Aromatase induced b...

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Autores: Rodríguez-Sanz M, García-Giralt N, Prieto-Alhambra D, Servitja S, Balcells S, Pecorelli R, Díez-Pérez A, Grinberg D, Tusquets I, Nogués X
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p10868
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10868
Access Level:acceso abierto
Palabra clave:CYP11A1, aromatase inhibitors, bone loss, breast cancer, genetic association
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spelling CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss.Rodríguez-Sanz MGarcía-Giralt NPrieto-Alhambra DServitja SBalcells SPecorelli RDíez-Pérez AGrinberg DTusquets INogués XCYP11A1, aromatase inhibitors, bone loss, breast cancer, genetic associationAromatase inhibitors (AIs) used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer cause diverse musculoskeletal side effects that include bone loss and its associated fracture. About half of the 391 patients treated with AIs in the Barcelona-Aromatase induced bone loss in early breast cancer cohort suffered a significant bone loss at lumbar spine (LS) and/or femoral neck (FN) after 2 years on AI-treatment. In contrast, up to one-third (19.6% LS, 38.6% FN) showed no decline or even increased bone density. The present study aimed to determine the genetic basis for this variability. SNPs in candidate genes involved in vitamin D and estrogen hormone-response pathways (CYP11A1, CYP17A1, HSD3B2, HSD17B3, CYP19A1, CYP2C19, CYP2C9, ESR1, DHCR7, GC, CYP2R1, CYP27B1, VDR and CYP24A1) were genotyped for association analysis with AI-related bone loss (AIBL). After multiple testing correction, 3 tag-SNPs (rs4077581, s11632698 and rs900798) located in the CYP11A1 gene were significantly associated (P<0.005) with FN AIBL at 2 years of treatment. Next, CYP11A1 expression in human fresh bone tissue and primary osteoblasts was demonstrated by RT-PCR. Both common isoforms of human cholesterol side-chain cleavage enzyme (encoded by CYP11A1 gene) were detected in osteoblasts by western blot. In conclusion, the genetic association of CYP11A1 gene with AIBL and its expression in bone tissue reveals a potential local function of this enzyme in bone metabolism regulation, offering a new vision of the steroidogenic ability of this tissue and new understanding of AI-induced bone loss.BIOSCIENTIFICA LTD2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10868JOURNAL OF MOLECULAR ENDOCRINOLOGYISSN: 09525041ISSNe: 14796813reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p108682026-05-27T12:37:41Z
dc.title.none.fl_str_mv CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss.
title CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss.
spellingShingle CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss.
Rodríguez-Sanz M
CYP11A1, aromatase inhibitors, bone loss, breast cancer, genetic association
title_short CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss.
title_full CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss.
title_fullStr CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss.
title_full_unstemmed CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss.
title_sort CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss.
dc.creator.none.fl_str_mv Rodríguez-Sanz M
García-Giralt N
Prieto-Alhambra D
Servitja S
Balcells S
Pecorelli R
Díez-Pérez A
Grinberg D
Tusquets I
Nogués X
author Rodríguez-Sanz M
author_facet Rodríguez-Sanz M
García-Giralt N
Prieto-Alhambra D
Servitja S
Balcells S
Pecorelli R
Díez-Pérez A
Grinberg D
Tusquets I
Nogués X
author_role author
author2 García-Giralt N
Prieto-Alhambra D
Servitja S
Balcells S
Pecorelli R
Díez-Pérez A
Grinberg D
Tusquets I
Nogués X
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CYP11A1, aromatase inhibitors, bone loss, breast cancer, genetic association
topic CYP11A1, aromatase inhibitors, bone loss, breast cancer, genetic association
description Aromatase inhibitors (AIs) used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer cause diverse musculoskeletal side effects that include bone loss and its associated fracture. About half of the 391 patients treated with AIs in the Barcelona-Aromatase induced bone loss in early breast cancer cohort suffered a significant bone loss at lumbar spine (LS) and/or femoral neck (FN) after 2 years on AI-treatment. In contrast, up to one-third (19.6% LS, 38.6% FN) showed no decline or even increased bone density. The present study aimed to determine the genetic basis for this variability. SNPs in candidate genes involved in vitamin D and estrogen hormone-response pathways (CYP11A1, CYP17A1, HSD3B2, HSD17B3, CYP19A1, CYP2C19, CYP2C9, ESR1, DHCR7, GC, CYP2R1, CYP27B1, VDR and CYP24A1) were genotyped for association analysis with AI-related bone loss (AIBL). After multiple testing correction, 3 tag-SNPs (rs4077581, s11632698 and rs900798) located in the CYP11A1 gene were significantly associated (P<0.005) with FN AIBL at 2 years of treatment. Next, CYP11A1 expression in human fresh bone tissue and primary osteoblasts was demonstrated by RT-PCR. Both common isoforms of human cholesterol side-chain cleavage enzyme (encoded by CYP11A1 gene) were detected in osteoblasts by western blot. In conclusion, the genetic association of CYP11A1 gene with AIBL and its expression in bone tissue reveals a potential local function of this enzyme in bone metabolism regulation, offering a new vision of the steroidogenic ability of this tissue and new understanding of AI-induced bone loss.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10868
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10868
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BIOSCIENTIFICA LTD
publisher.none.fl_str_mv BIOSCIENTIFICA LTD
dc.source.none.fl_str_mv JOURNAL OF MOLECULAR ENDOCRINOLOGY
ISSN: 09525041
ISSNe: 14796813
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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