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

Abstract

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 (ERalpha) and beta (ERbeta) 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 ERalpha and ERbeta differed between papillary and anaplastic cancer. Upon E2 treatment, the level of ERalpha increased in the nuclei of papillary cancer cells but ERbeta remained unchanged. The level of mitochondrial ERbeta surpassed that of ERalpha in anaplastic cancer cells. The different locations of ERalpha and ERbeta 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 ERalpha and ERbeta may account for the different pathogenesis of thyroid papillary and anaplastic cancers.

The role of oestrogen receptor α in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2

“…Epidemiological, translational and clinical evidence suggests a role for oestrogens in the development of thyroid cancer (Kishino et al 1997, Rossing et al 2000, Lee et al 2003, Zeng et al 2008. Recent reports suggest that oestrogen can increase ERa expression in non-anaplastic papillary cancer cells, increase cellular proliferation and inhibit pro-apoptotic protein expression.…”

“…The oestrogen receptor (ER) is encoded for by two genes, ERa and ERb. Though both isoforms of the receptor have been identified in human thyroid tumour tissue, it is ERa that has been associated with increased oestrogen-dependent cell proliferation (Zeng et al 2008). Oestrogen can also mediate its effects independently of its classic nuclear receptor.…”

Expression of the estrogen receptor α, progesterone receptor and epidermal growth factor receptor in papillary thyroid carcinoma tissues

“…Experimental studies have revealed that estrogen affects PTC development by interacting with ER at the level of target thyroid cells, thereby promoting the proliferation of mutated follicular cells (23). In addition, several different thyroid cancer cell lines have been revealed Tumor size, n (%) to express ER (24)(25)(26), and the proliferation of these cells was stimulated by ERα agonists, and downregulated by ERβ agonists (23). Consistently, the present study revealed that the expression of ERα is increased in PTC tissues, compared with the expression in NTG tissues.…”

Immunoanalysis indicates that the sodium iodide symporter is not overexpressed in intracellular compartments in thyroid and breast cancers

“…No specific staining was expected using anti-CD45 antibodies. ER was also expected to be absent from thyroid cells, but a recent publication suggests that ER is expressed in thyroid cancer lines and could contribute to the development of thyroid carcinomas (33). A specific immunostaining of ER is expected to show a different pattern (as nuclear localization).…”