contributions of oestrogen receptor isoforms to the development of papillary and anaplastic thyroid carcinomas

Oestrogen (E2) is known to promote the proliferation of thyroid papillary carcinoma cells (KAT5). However, the molecular mechanism responsible is not well understood. In the study reported herein, the localization of ER alpha (ERα) and beta (ERβ) in KAT5 and anaplastic carcinoma cells (FRO) was stud...

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Bibliographic Details
Published in:The Journal of pathology 2008-03, Vol.214 (4), p.425-433
Main Authors: Zeng, Q, Chen, GG, Vlantis, AC, Tse, GM, van Hasselt, CA
Format: Article
Language:English
Subjects:
apoptosis
Apoptosis Inducing Factor - metabolism
bcl-2-Associated X Protein - metabolism
Biological and medical sciences
Carcinoma - metabolism
Carcinoma - pathology
Carcinoma, Papillary - metabolism
Carcinoma, Papillary - pathology
Cell Death
Cell Proliferation - drug effects
Cytochromes c - metabolism
Endocrinopathies
Estradiol - analogs & derivatives
Estradiol - pharmacology
Estrogen Antagonists - pharmacology
Estrogen Receptor alpha - metabolism
Estrogen Receptor alpha - physiology
Estrogen Receptor beta - metabolism
Estrogen Receptor beta - physiology
Estrogens - pharmacology
Humans
Investigative techniques, diagnostic techniques (general aspects)
Malignant tumors
Medical sciences
Neoplasm Proteins - metabolism
oestrogen receptors
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
proliferation
Receptors, Estrogen - metabolism
Receptors, Estrogen - physiology
Subcellular Fractions - metabolism
thyroid cancer
Thyroid Neoplasms - metabolism
Thyroid Neoplasms - pathology
Thyroid. Thyroid axis (diseases)
Tumor Cells, Cultured
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Summary:Oestrogen (E2) is known to promote the proliferation of thyroid papillary carcinoma cells (KAT5). However, the molecular mechanism responsible is not well understood. In the study reported herein, the localization of ER alpha (ERα) and beta (ERβ) in KAT5 and anaplastic carcinoma cells (FRO) was studied by immunofluorescence staining and by immunoblotting the proteins in subcellular fractions. Cell proliferation and apoptosis were also determined together with the expression of relevant proteins. The pattern of the subcellular localization of ERα and ERβ differed between papillary and anaplastic cancer. Upon E2 treatment, the level of ERα increased in the nuclei of papillary cancer cells but ERβ remained unchanged. The level of mitochondrial ERβ surpassed that of ERα in anaplastic cancer cells. The different locations of ERα and ERβ in KAT5 and FRO agreed with the finding that E2 promoted the proliferation of KAT5 but inhibited or did not affect that of FRO cells, and with the proposed functions of these two receptors. E2 inhibited the level of Bax in the mitochondria of papillary cancer, followed by a decrease of cytochrome c and/or apoptosis-inducing factor (AIF) release from the mitochondria into the cytosol. However, in anaplastic cancer, E2 promoted the expression of Bax in the mitochondria and the release of cytochrome c and/or AIF from mitochondria into the cytosol. Our results may explain the differences in epidemiology and responses to anti-tumour therapy between papillary and anaplastic cancer in terms of the subcellular localization of ER isoforms. In conclusion, the findings provide evidence to support the observation that E2 is an important factor in the development of thyroid cancer. The subcellular localization of ERα and ERβ may account for the different pathogenesis of thyroid papillary and anaplastic cancers. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
ISSN:0022-3417
1096-9896
DOI:10.1002/path.2297