Concomitant high expression of ERα36, EGFR and HER2 is associated with aggressive behaviors of papillary thyroid carcinomas

Dai, Yujie; Qiu, Yulan; Jiang, Rong; Xu, Man; Zhao, Le; Chen, George G.; Liu, Zhimin

doi:10.1038/s41598-017-12478-1

Cited by 23 publications

(29 citation statements)

References 49 publications

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“…Incidence of ER expression in the current study was at par with other published reports, which ranged from 17-54% [1,3,5,[14][15][16][17]. ERα expression has been correlated with tumor virulence, large tumors, extrathyroidal invasion, distant metastases, and reduced DFS [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. But on the contrary, there are reports, which showed that ERα and cosecretary proteins expression are positively associated with well-differentiated tumors and inversely with disease recurrence [1,3].…”

Section: Discussioncontrasting

confidence: 62%

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Distribution and Prognostic Significance of Estrogen Receptorα(ERα), Estrogen Receptorβ(ERβ), and Human Epidermal Growth Factor Receptor 2 (HER-2) in Thyroid Carcinoma

Mishra

Kumari

Jha

et al. 2020

Journal of Thyroid Research

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Purpose. The primary aim of this study was to determine the incidence of estrogen receptor α (ERα), estrogen receptor β (ERβ), and human epidermal growth factor receptor 2 (HER-2) expression in various subtypes of thyroid carcinoma (TC) of follicular origin and the secondary aim was to correlate the expression with various clinicopathologic prognostic factors. Methods. Immunohistochemistry analysis was performed on archival paraffin-embedded tissue sections (1991–2016). ERα, ERβ, and HER-2 expressions were correlated with clinicopathologic prognostic factors, disease recurrence, and overall survival (OS). Results. A total of 264 TC patients were included in the study. Incidences of ERα, ERβ, and HER-2 were 8.1 vs 16.3 vs 13.9% p=0.15, 26.6 vs 11.5 vs 36.1% p=0.002, and 12.9 vs 2.9 vs 0% p=0.003 in papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and poorly differentiated thyroid carcinoma (PDTC), respectively. Overall ERα had significant correlation with distant metastases (0.038) and in case of PDTC with multicentricity p=0.037. ERβ had significant correlation with lymph node metastases p=0.023 in FTC. HER-2 correlated with tumor size p=0.027 only on univariate analysis. OS did not correlate with expression of any receptor. Conclusion. ERα, ERβ, and HER-2 have differential expression and prognostic implications in different TC subtypes.

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Section: Discussioncontrasting

confidence: 62%

Section: Discussionsupporting

confidence: 57%

Distribution and Prognostic Significance of Estrogen Receptorα(ERα), Estrogen Receptorβ(ERβ), and Human Epidermal Growth Factor Receptor 2 (HER-2) in Thyroid Carcinoma

Mishra

Kumari

Jha

et al. 2020

Journal of Thyroid Research

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“…Additionally, data suggest that blocking EGFR can effectively increase the antitumor activity of selumetinib in triple-negative breast cancer, which may be related to the effect of this combination on the activation of extracellular signal-regulated kinase 1/2 and AKT [ 29 ]. In PTC, EGFR was demonstrated to upregulate in about 55% of PTCs and is correlated with aggressive behaviors of PTC [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

ciRS-7 Promotes the Proliferation and Migration of Papillary Thyroid Cancer by Negatively Regulating the miR-7/Epidermal Growth Factor Receptor Axis

Han

Guo

Wei

et al. 2020

BioMed Research International

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Purpose. The incidence of papillary thyroid cancer (PTC) is increasing, and traditional diagnostic methods are unsatisfactory. Therefore, identifying novel prognostic markers is very important. ciRS-7 has been found to play an important role in many cancers, but its role in PTC has not been reported. This study was performed to evaluate the biological role and mechanism of ciRS-7 in PTC. Material and Methods. The expression of ciRS-7 in PTC tissues and the matched adjacent tissues was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The PTC cell lines (TPC-1 and BCPAP) were used to evaluate the role of ciRS-7. ciRS-7-siRNA and overexpression plasmid were constructed and transfected into PTC cells. A CCK-8 assay and colony formation assay were performed to explore the effects of ciRS-7 on cell proliferation. Annexin V/PI staining and FACS detection were used to detect cell apoptosis. Wound healing assay was performed to detect cell migration. A transwell assay was conducted to explore the effects of ciRS-7 on invasion and migration. Western blotting was performed to evaluate protein expression. The luciferase reporter system was used to determine the underlying mechanism of miR-7. Result. ciRS-7 was highly expressed in PTC tissues and cell lines compared with the corresponding controls. In vitro study showed that ciRS-7 silencing suppressed proliferation, migration, and invasion of TPC-1 and BCPAP. Mechanistically, the effects of ciRS-7 on invasion and migration may be related to epithelial-mesenchymal transition (EMT). ciRS-7 silencing could attenuate effects on PTC cells induced by miR-7 knockdown. Epidermal growth factor receptor (EGFR), which was demonstrated to be a target of miR-7, decreased significantly in ciRS-7-siRNA PTC cells. Overexpression of EGFR also attenuated effects of PTC cells induced by silencing ciRS-7. Conclusion. ciRS-7 was significantly upregulated in PTC tissues, and it promoted the progression of PTC by regulating the miR-7/EGFR axis. ciRS-7 is a promising prognostic biomarker and therapeutic target in PTC.

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“…Papillary thyroid cancer (PTC) represents about 80% of malignant thyroid tumors and is three times more common in women than in men suggesting a critical role of estrogen in its occurrence and development ( 32 – 34 ). Dai et al, analyzed the expression levels of ERα36, in association with the epidermal growth factor receptor (EGFR) and HER2, in PTCs, nodular hyperplasias and normal thyroid tissues ( 35 ). The results obtained highlight the existence of a significant correlation between the high levels of expression of ERα36 in PTC tissues and the progression and increase of tumor metastases.…”

Section: Erα36 In Different Types Of Tumorsmentioning

confidence: 99%

A Role for Estrogen Receptor alpha36 in Cancer Progression

2020

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Estrogen receptor α (ERα) functions as a ligand dependent transcription factor that directly binds specific estrogen responsive elements, thus regulating the transcription of estrogen sensitive genes. ERα has also been shown to be associated with the plasma membrane (membrane associated ERα, mERα), concentrated in lipid rafts, plasma membrane microdomains with a distinct lipid composition, where it transduces membrane-initiated estrogen-dependent activation of the mitogen-activated protein (MAP) kinase signaling pathway. Two isoforms of ERα have been described: the “traditional” ERα66 (66 kDa) and a lower molecular weight variant: the ERα46 (46 kDa). More recently, a novel ERα variant with a molecular mass of 36 kDa (ERα36) has been discovered. Notably, ERα36 has been found expressed in different human tumor cells, including both ER- positive and ER- negative breast cancer cells. Estrogen signaling at the cell membrane via ERα36 appears as capable of activating multiple pathways of importance for cancer aggressiveness and metastatic potential. The presence of serum autoantibodies reacting with mERα (anti-ERα Abs) in a large percentage of patients with breast cancer has recently been reported by our group. These anti-ERα Abs seem to act as estrogen agonists rapidly triggering MAP kinase pathway activation thus inducing tumor cell proliferation and overcoming cell resistance to anti-estrogen drug tamoxifen. In this review, we describe the involvement of ERα36 in different tumors. We also report the potential pathogenetic activity of anti-ERα Abs and their implication in drug resistance.

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Concomitant high expression of ERα36, EGFR and HER2 is associated with aggressive behaviors of papillary thyroid carcinomas

Cited by 23 publications

References 49 publications

Distribution and Prognostic Significance of Estrogen Receptorα(ERα), Estrogen Receptorβ(ERβ), and Human Epidermal Growth Factor Receptor 2 (HER-2) in Thyroid Carcinoma

Distribution and Prognostic Significance of Estrogen Receptorα(ERα), Estrogen Receptorβ(ERβ), and Human Epidermal Growth Factor Receptor 2 (HER-2) in Thyroid Carcinoma

ciRS-7 Promotes the Proliferation and Migration of Papillary Thyroid Cancer by Negatively Regulating the miR-7/Epidermal Growth Factor Receptor Axis

A Role for Estrogen Receptor alpha36 in Cancer Progression

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