The role of oestrogen receptor {alpha} in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2.
Authors
Kavanagh, Dara OMcIlroy, Marie
Myers, Eddie
Bane, Fiona
Crotty, Thomas B
McDermott, E
Hill, Arnold D
Young, Leonie S
Affiliation
School of Medicine and Medical Science, UCD Conway Institute, St Vincent's, University Hospital and University College Dublin, Dublin 4, Ireland.Issue Date
2012-02-01T10:33:10ZMeSH
Adenocarcinoma, Follicular/*etiology/metabolism/mortalityAdolescent
Adult
Aged
Aged, 80 and over
Carcinoma/etiology/metabolism/mortality
Case-Control Studies
Child
Child, Preschool
Co-Repressor Proteins/metabolism/physiology
Estrogen Receptor alpha/metabolism/*physiology
Female
Humans
Male
Middle Aged
Receptor Protein-Tyrosine Kinases/metabolism/physiology
Receptor, erbB-2/metabolism/*physiology
Survival Analysis
Thyroid Neoplasms/*etiology/metabolism/mortality
Trans-Activators/metabolism/physiology
Transcription Factors/metabolism/*physiology
Tumor Cells, Cultured
Young Adult
Metadata
Show full item recordCitation
Endocr Relat Cancer. 2010 Feb 18;17(1):255-64. Print 2010 Mar.Journal
Endocrine-related cancerDOI
10.1677/ERC-09-0216PubMed ID
20032008Abstract
Epidemiological, clinical, and molecular studies suggest a role for oestrogen in thyroid cancer. How oestrogen mediates its effects and the consequence of it on clinical outcome has not been fully elucidated. The participation of coregulatory proteins in modulating oestrogen receptor (ER) function and input of crosstalk with the tyrosine kinase receptor HER2 was investigated. Oestrogen induced cell proliferation in the follicular thyroid cancer (FTC)-133 cells, but not in the anaplastic 8305C cell line. Knockdown of the coactivator steroid receptor coactivator (SRC)-1 inhibited FTC-133 basal, but not oestrogen induced, cell proliferation. Oestrogen also increased protein expression of SRC-1 and the ER target gene cyclin D1 in the FTC-133 cell line. ERalpha, ERbeta, the coregulatory proteins SRC-1 and nuclear corepressor (NCoR), and the tyrosine kinase receptor HER2 were localised by immunohistochemistry and immnofluorescence in paraffin-embedded tissue from thyroid tumour patients (n=111). ERalpha was colocalised with both SRC-1 and NCoR to the nuclei of the tumour epithelial cells. Expression of ERalpha and NCoR was found predominantly in non-anaplastic tumours and was significantly associated with well-differentiated tumours and reduced incidence of disease recurrence. In non-anaplastic tumours, HER2 was significantly associated with SRC-1, and these proteins were associated with poorly differentiated tumours, capsular invasion and disease recurrence. Totally, 87% of anaplastic tumours were positive for SRC-1. Kaplan-Meier estimates of disease-free survival indicated that in thyroid cancer, SRC-1 strongly correlates with reduced disease-free survival (P<0.001), whereas NCoR predicted increased survival (P<0.001). These data suggest opposing roles for the coregulators SRC-1 and NCoR in thyroid tumour progression.Language
engISSN
1479-6821 (Electronic)1351-0088 (Linking)
ae974a485f413a2113503eed53cd6c53
10.1677/ERC-09-0216
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