Enhanced expression of the PDGFR/Abl signaling pathway in aromatase inhibitor-resistant breast cancer.
Ann Oncol
; 24(1): 126-33, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-22865780
ABSTRACT
BACKGROUND:
We have found that the platelet-derived growth factor receptor (PDGFR)/Abl signaling pathway is up-regulated as a determinant of the acquisition of resistance to estrogen deprivation in vitro. We aimed to determine its clinical relevance in aromatase inhibitor (AI)-resistant breast cancer. PATIENTS ANDMETHODS:
We identified a cohort of 45 patients with estrogen receptor-positive breast cancer who had been treated with an AI, subsequently relapsed and had biopsy material available from both the presentation and post-AI recurrent lesion. PDGFRα, PDGFRß and Abl expression was assessed in formalin-fixed paraffin-embedded sections.RESULTS:
Tumor protein expression of PDGFRα (1.39-fold, P=0.0065), PDGFRß (4.32-fold, P=0.006) and Abl (1.8-fold, P=0.001) was increased at the point of relapse. Tumor and stromal expression of PDGFRα as well as PDGFRß was significantly correlated in pre-treatment and relapse samples. High post-treatment tumor and stromal PDGFRß levels were associated with a short time to treatment failure (TTF). Expression of PDGFRα in relapsing tumor specimens was correlated with Abl expression and Ki67 levels. Furthermore, changes in Abl correlated significantly with changes in ER expression.CONCLUSIONS:
These clinical data support a role for enhanced PDGF/Abl signaling in AI-resistant disease and provide a rationale for targeting the pathway in endocrine-resistant breast cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Transdução de Sinais
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Proteínas Oncogênicas v-abl
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Receptores do Fator de Crescimento Derivado de Plaquetas
/
Inibidores da Aromatase
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article