ERβ decreases the invasiveness of triple-negative breast cancer cells by regulating mutant p53 oncogenic function

Bado, Igor; Nikolos, Fotis; Rajapaksa, Gayani; Gustafsson, Jan‐Åke; Thomas, Christoforos

doi:10.18632/oncotarget.7300

Cited by 43 publications

(64 citation statements)

References 55 publications

(87 reference statements)

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“…Knockdown of p63 reversed the effect of ERb1 on cell cycle of chemotherapy-treated NSCLC cells, indicating its involvement in the mechanism of ERb1 action. Moreover, we previously showed that ERb1 interacts with p63 to promote upregulation of p63 target genes in breast cancer cells (46). Among these, Cyclin G2 (CCNG2) is an estrogenregulated gene that is activated by p63 to control the G 2 -M cellcycle checkpoint (61,62).…”

Section: Discussionmentioning

confidence: 99%

“…One of the mechanisms by which estrogen receptors elicit their tumor-associated functions involves their transcriptional cooperation with the p53-family proteins p53 and p63 (46,47). To further elucidate the molecular pathways that mediate the effect of ERb1 on chemotherapy response of NSCLC cells, we investigated whether ERb1 acts through p63 in H1299 cells.…”

Section: Erb1 Synergizes With P63 To Enhance the Chemosensitivity Of mentioning

confidence: 99%

“…As a transcription factor, p63 affects the expression of several genes that regulate cellcycle progression including Cyclin G2 (CCNG2) that activates the G 2 -M cell-cycle checkpoint (48). It was previously shown that CCNG2 is upregulated by ERb1 (46) and repressed by ERa and estrogen in cancer cells (49). We initially examined whether disruption of p63 expression alters the effect of ERb1 on chemotherapy response of H1299 cells.…”

Section: Erb1 Synergizes With P63 To Enhance the Chemosensitivity Of mentioning

confidence: 99%

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ERβ Sensitizes NSCLC to Chemotherapy by Regulating DNA Damage Response

Nikolos

Thomas

Bado

et al. 2018

Molecular Cancer Research

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The expression of wild-type estrogen receptor β (ESR2/ERβ1) correlates with clinical outcome in patients with non-small cell lung cancer (NSCLC). However, the molecular mechanism that accounts for this association is currently poorly understood. ERβ1 was previously linked to chemotherapy response in patients with breast cancer and in breast cancer cells. The effect of the receptor in NSCLC cells after chemotherapy treatment, a common remedy for advanced NSCLC, has not been studied. Here, upregulation of ERβ1 increases the sensitivity of NSCLC cells to treatment with doxorubicin and etoposide. This effect was primarily observed in p53-defecient NSCLC cells. In these cells, ERβ1 either enhanced G-M cell-cycle arrest by activating the checkpoint kinase 1 (Chk1) and altering downstream signaling or induced apoptosis. The expression of p63 target genes that control G-M checkpoint activation was altered by ERβ1 suggesting an ERβ1-p63 transcriptional cooperation in lung cancer cells that affects DNA damage response (DDR). These results suggest involvement of ERβ1 in the mechanism that regulates DNA damage response in NSCLC cells and support the potential predictive and therapeutic value of the receptor in clinical management of the disease. This study demonstrating the impact of ERβ1 on chemosensitivity of NSCLC cells suggests the predictive value of the receptor for successful response of tumors to chemotherapy and the potential benefit of chemotherapy-treated patients from the use of ER ligands. .

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Section: Discussionmentioning

confidence: 99%

Section: Erb1 Synergizes With P63 To Enhance the Chemosensitivity Of mentioning

confidence: 99%

Section: Erb1 Synergizes With P63 To Enhance the Chemosensitivity Of mentioning

confidence: 99%

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ERβ Sensitizes NSCLC to Chemotherapy by Regulating DNA Damage Response

Nikolos

Thomas

Bado

et al. 2018

Molecular Cancer Research

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“…Intriguingly, the ERβ isoform displays strong regulatory effects on EMT/MET factors and metastasis in breast cancer. ERβ expression was enough to induce E-cadherin expression in basal-like ERα-negative cells, suggesting anti-metastatic functions of the receptor in breast cancer 154 , 155 . Despite significant progress, the role of ERs in bone metastasis is still uncertain.…”

Section: Ers In Breast Cancermentioning

confidence: 96%

Estrogen receptors in breast and bone: from virtue of remodeling to vileness of metastasis

et al. 2017

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Bone metastasis is a prominent cause of morbidity and mortality in cancer. High rates of bone colonization in breast cancer, especially in the subtype expressing estrogen receptors (ERs), suggests tissue-specific proclivities for metastatic tumor formation. The mechanisms behind this subtype-specific organ-tropism remains largely elusive. Interestingly, as the major driver of ER+ breast cancer, ERs also play important roles in bone development and homeostasis. Thus, any agents targeting ER will also inevitably affect the microenvironment, i.e., the osteoblasts and osteoclasts. Yet, how such microenvironmental effects are integrated with direct therapeutic responses of cancer cells remain poorly understood. Recent findings on ER mutations, especially their enrichment in bone metastasis, raised even more provocative questions on the role of ER in cancer-bone interaction. In this review, we evaluate the importance of estrogen receptors (ERs) in bone metastasis and discuss new avenues of investigation for bone metastasis treatment based on current knowledge.

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“…On the other hand, some studies discovered ERβ to be a better prognostic indicator in patients with breast cancer 51–53. Ström et al 51 showed that the growth of luminal T47D cells expressing mutant p53 was inhibited by ERβ, both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Characteristics, behaviour and role of biomarkers in metastatic triple-negative breast cancer

Goto¹,

Thike

Ong

et al. 2019

J Clin Pathol

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AimsCharacterising the factors responsible for metastatic triple-negative breast cancer (TNBC) is of significant importance, considering its high mortality rate and scant data. In this study, we evaluated the characteristics, clinical behaviour and role of biomarkers (androgen receptor (AR), oestrogen receptor beta (ERβ) and p53) in metastatic TNBC.MethodsImmunohistochemistry was performed for AR, ERβ and p53 on 125 primary TNBCs with known metastasis and correlated with clinicopathological parameters and outcome. AR and p53 mRNA profiling was also carried out on 34 tumours from the same series and correlated with outcomes.ResultsIn this cohort, grade 3 and pT2 tumours predominated. The most common site for metastasis was the lung and pleura (41, 32.8%), and 15 (12.0%) cases demonstrated metastasis in multiple sites. Among these, 92% of tumours metastasised without preceding local recurrences. Five- and ten-year overall survival (OS) rates were 27% and 7.2%, while 5- and 10- year survival rates after metastasis were 9.6% and 3.2% respectively. AR, ERβ and p53 protein expressions were observed in 16%, 96.8% and 58.1% of tumours, respectively. A combinational phenotype of AR-ERβ+p53+ tumours was associated with poorer OS (HR 1.543, 95%CI 1.030 to 2.310, p=0.035). Higher AR mRNA levels were significantly associated with favourable OS (p=0.015) and survival after metastasis (p=0.027).ConclusionsMetastatic TNBC harboured aggressive behaviour and displayed predominantly visceral metastasis with most metastatic events occurring without intervening local recurrences. A combinational phenotype of AR-ERβ+p53+ was significantly associated with poorer OS.

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ERβ decreases the invasiveness of triple-negative breast cancer cells by regulating mutant p53 oncogenic function

Cited by 43 publications

References 55 publications

ERβ Sensitizes NSCLC to Chemotherapy by Regulating DNA Damage Response

ERβ Sensitizes NSCLC to Chemotherapy by Regulating DNA Damage Response

Estrogen receptors in breast and bone: from virtue of remodeling to vileness of metastasis

Characteristics, behaviour and role of biomarkers in metastatic triple-negative breast cancer

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