The role of oestrogen receptor {alpha} in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2.

Hdl Handle:
http://hdl.handle.net/10147/207623
Title:
The role of oestrogen receptor {alpha} in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2.
Authors:
Kavanagh, Dara O; McIlroy, 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.
Citation:
Endocr Relat Cancer. 2010 Feb 18;17(1):255-64. Print 2010 Mar.
Journal:
Endocrine-related cancer
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207623
DOI:
10.1677/ERC-09-0216
PubMed ID:
20032008
Abstract:
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:
eng
MeSH:
Adenocarcinoma, Follicular/*etiology/metabolism/mortality; Adolescent; 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
ISSN:
1479-6821 (Electronic); 1351-0088 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorKavanagh, Dara Oen_GB
dc.contributor.authorMcIlroy, Marieen_GB
dc.contributor.authorMyers, Eddieen_GB
dc.contributor.authorBane, Fionaen_GB
dc.contributor.authorCrotty, Thomas Ben_GB
dc.contributor.authorMcDermott, Een_GB
dc.contributor.authorHill, Arnold Den_GB
dc.contributor.authorYoung, Leonie Sen_GB
dc.date.accessioned2012-02-01T10:33:10Z-
dc.date.available2012-02-01T10:33:10Z-
dc.date.issued2012-02-01T10:33:10Z-
dc.identifier.citationEndocr Relat Cancer. 2010 Feb 18;17(1):255-64. Print 2010 Mar.en_GB
dc.identifier.issn1479-6821 (Electronic)en_GB
dc.identifier.issn1351-0088 (Linking)en_GB
dc.identifier.pmid20032008en_GB
dc.identifier.doi10.1677/ERC-09-0216en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207623-
dc.description.abstractEpidemiological, 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAdenocarcinoma, Follicular/*etiology/metabolism/mortalityen_GB
dc.subject.meshAdolescenten_GB
dc.subject.meshAdulten_GB
dc.subject.meshAgeden_GB
dc.subject.meshAged, 80 and overen_GB
dc.subject.meshCarcinoma/etiology/metabolism/mortalityen_GB
dc.subject.meshCase-Control Studiesen_GB
dc.subject.meshChilden_GB
dc.subject.meshChild, Preschoolen_GB
dc.subject.meshCo-Repressor Proteins/metabolism/physiologyen_GB
dc.subject.meshEstrogen Receptor alpha/metabolism/*physiologyen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshReceptor Protein-Tyrosine Kinases/metabolism/physiologyen_GB
dc.subject.meshReceptor, erbB-2/metabolism/*physiologyen_GB
dc.subject.meshSurvival Analysisen_GB
dc.subject.meshThyroid Neoplasms/*etiology/metabolism/mortalityen_GB
dc.subject.meshTrans-Activators/metabolism/physiologyen_GB
dc.subject.meshTranscription Factors/metabolism/*physiologyen_GB
dc.subject.meshTumor Cells, Cultureden_GB
dc.subject.meshYoung Adulten_GB
dc.titleThe role of oestrogen receptor {alpha} in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2.en_GB
dc.contributor.departmentSchool of Medicine and Medical Science, UCD Conway Institute, St Vincent's, University Hospital and University College Dublin, Dublin 4, Ireland.en_GB
dc.identifier.journalEndocrine-related canceren_GB
dc.description.provinceLeinster-

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