FOXA1 levels are decreased in pleural breast cancer metastases after adjuvant endocrine therapy, and this is associated with poor outcome

Autor: Rui Henrique, Annelot van Rossum, Jelle Wesseling, Marjolein Droog, Karianne Schuurman, Wilbert Zwart, Sabine C. Linn, Sofia Salta, Michel M. van den Heuvel, Willemijne A. M. E. Schrijver, Paul J. van Diest, Cathy B. Moelans, Carmen Jerónimo
Přispěvatelé: Chemical Biology
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Oncology
Male
Cancer Research
Hepatocyte Nuclear Factor 3-alpha/metabolism
SDG 3 – Goede gezondheid en welzijn
0302 clinical medicine
breast cancer metastasis
80 and over
Neoplasm Metastasis
Research Articles
Adjuvant
Aged
80 and over
GATA3
acquired endocrine resistance
General Medicine
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Metastatic breast cancer
Primary tumor
Neoplasm Proteins
Survival Rate
Chemotherapy
Adjuvant
030220 oncology & carcinogenesis
Molecular Medicine
Female
pleural effusions
Research Article
Hepatocyte Nuclear Factor 3-alpha
Adult
medicine.medical_specialty
medicine.drug_class
Pleural Neoplasms
Breast Neoplasms
Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9]
lcsh:RC254-282
Disease-Free Survival
03 medical and health sciences
Breast cancer
Breast Neoplasms/drug therapy
SDG 3 - Good Health and Well-being
Internal medicine
medicine
Genetics
Journal Article
Endocrine system
Humans
Chemotherapy
Neoplasm Proteins/metabolism
Survival rate
Aged
Pleural Neoplasms/drug therapy
business.industry
medicine.disease
030104 developmental biology
Estrogen
FOXA1
business
Zdroj: Molecular Oncology
Molecular Oncology, 12, 1884-1894
Molecular Oncology, 12(11), 1884. Elsevier
Molecular Oncology, Vol 12, Iss 11, Pp 1884-1894 (2018)
Molecular Oncology, 12, 11, pp. 1884-1894
Molecular Oncology, 12(11), 1884-1894. Elsevier
ISSN: 1878-0261
1574-7891
Popis: Contains fulltext : 200105.pdf (Publisher’s version ) (Open Access) Estrogen receptor-alpha (ERalpha)-positive breast cancer is often treated with antihormonal regimens. However, resistance to treatment is common, leading to metastatic disease. ERalpha activity requires the functional involvement of pioneer factors FOXA1 and GATA3, which enable ERalpha-chromatin binding and are crucial for ERalpha-driven cell proliferation. FOXA1 was found increased in metastatic breast cancers in relation to the primary tumor, but a comprehensive clinical assessment thereof, in relation to different metastatic sites and endocrine therapy usage, is currently lacking. Prior cell line-based reports, however, have revealed that FOXA1 is required for tamoxifen-resistant tumor cell proliferation. We studied expression levels of ERalpha, GATA3, and FOXA1 by immunohistochemistry in samples from both primary tumors and various metastatic sites. For all factors, expression levels varied between the metastatic sites. For pleural metastases, strong variation was found in FOXA1 and GATA3 levels. Although GATA3 levels remained unaltered between primary breast cancer and pleural metastases, FOXA1 levels were reduced exclusively in metastases of patients who received endocrine therapies in the adjuvant setting, even though ERalpha was still expressed. Importantly, decreased FOXA1 levels in pleural metastases correlated with hormone irresponsiveness in the palliative setting, while no such correlation was found for GATA3. With this, we show divergent clinical correlations of the two ERalpha pioneer factors FOXA1 and GATA3 in metastatic breast cancer, where endocrine therapy resistance was associated with decreased FOXA1 levels in pleural metastases. 01 november 2018
Databáze: OpenAIRE
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