scholarly journals ERβ overexpression results in endocrine therapy resistance and poor prognosis in postmenopausal ERα-positive breast cancer patients

2016 ◽  
Vol 11 (2) ◽  
pp. 1531-1536 ◽  
Author(s):  
LIYING GUO ◽  
YU ZHANG ◽  
DILIMINA YILAMU ◽  
SHA LIU ◽  
CHENMING GUO
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Poor Prognosis ◽  
Therapy Resistance ◽  
Breast Cancer Patients ◽  
Endocrine Therapy Resistance ◽  
Positive Breast Cancer

scholarly journals TRIM47 activates NF-κB signaling via PKC-ε/PKD3 stabilization and contributes to endocrine therapy resistance in breast cancer

2021 ◽  
Vol 118 (35) ◽  
pp. e2100784118
Author(s):  
Kotaro Azuma ◽  
Kazuhiro Ikeda ◽  
Takashi Suzuki ◽  
Kenjiro Aogi ◽  
Kuniko Horie-Inoue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Kinase ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Cancer Biology ◽  
Therapy Resistance ◽  
Clinical Samples ◽  
Breast Cancer Patients ◽  
Endocrine Therapy Resistance ◽  
Mcf 7

Increasing attention has been paid to roles of tripartite motif–containing (TRIM) family proteins in cancer biology, often functioning as E3 ubiquitin ligases. In the present study, we focus on a contribution of TRIM47 to breast cancer biology, particularly to endocrine therapy resistance, which is a major clinical problem in breast cancer treatment. We performed immunohistochemical analysis of TRIM47 protein expression in 116 clinical samples of breast cancer patients with postoperative endocrine therapy using tamoxifen. Our clinicopathological study showed that higher immunoreactivity scores of TRIM47 were significantly associated with higher relapse rate of breast cancer patients (P = 0.012). As functional analyses, we manipulated TRIM47 expression in estrogen receptor–positive breast cancer cells MCF-7 and its 4-hydroxytamoxifen (OHT)-resistant derivative OHTR, which was established in a long-term culture with OHT. TRIM47 promoted both MCF-7 and OHTR cell proliferation. MCF-7 cells acquired tamoxifen resistance by overexpressing exogenous TRIM47. We found that TRIM47 enhances nuclear factor kappa-B (NF-κB) signaling, which further up-regulates TRIM47. We showed that protein kinase C epsilon (PKC-ε) and protein kinase D3 (PKD3), known as NF-κB–activating protein kinases, are directly associated with TRIM47 and stabilized in the presence of TRIM47. As an underlying mechanism, we showed TRIM47-dependent lysine 27–linked polyubiquitination of PKC-ε. These results indicate that TRIM47 facilitates breast cancer proliferation and endocrine therapy resistance by forming a ternary complex with PKC-ε and PKD3. TRIM47 and its associated kinases can be a potential diagnostic and therapeutic target for breast cancer refractory to endocrine therapy.

scholarly journals ESR1-Stabilizing Long Noncoding RNA TMPO-AS1 Promotes Hormone-Refractory Breast Cancer Progression

2019 ◽  
Vol 39 (23) ◽  
Author(s):  
Yuichi Mitobe ◽  
Kazuhiro Ikeda ◽  
Takashi Suzuki ◽  
Kiyoshi Takagi ◽  
Hidetaka Kawabata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Cancer Progression ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

ABSTRACT Acquired endocrine therapy resistance is a significant clinical problem for breast cancer patients. In recent years, increasing attention has been paid to long noncoding RNA (lncRNA) as a critical modulator for cancer progression. Based on RNA-sequencing data of breast invasive carcinomas in The Cancer Genome Atlas database, we identified thymopoietin antisense transcript 1 (TMPO-AS1) as a functional lncRNA that significantly correlates with proliferative biomarkers. TMPO-AS1 positivity analyzed by in situ hybridization significantly correlates with poor prognosis of breast cancer patients. TMPO-AS1 expression was upregulated in endocrine therapy-resistant MCF-7 cells compared with levels in parental cells and was estrogen inducible. Gain and loss of TMPO-AS1 experiments showed that TMPO-AS1 promotes the proliferation and viability of estrogen receptor (ER)-positive breast cancer cells in vitro and in vivo. Global expression analysis using a microarray demonstrated that TMPO-AS1 is closely associated with the estrogen signaling pathway. TMPO-AS1 could positively regulate estrogen receptor 1 (ESR1) mRNA expression by stabilizing ESR1 mRNA through interaction with ESR1 mRNA. Enhanced expression of ESR1 mRNA by TMPO-AS1 could play a critical role in the proliferation of ER-positive breast cancer. Our findings provide a new insight into the understanding of molecular mechanisms underlying hormone-dependent breast cancer progression and endocrine resistance.

scholarly journals Activated HER-receptors in predicting outcome of ER-positive breast cancer patients treated with adjuvant endocrine therapy

The Breast ◽  
2012 ◽  
Vol 21 (5) ◽  
pp. 662-668 ◽  
Author(s):  
Mathilde S. Larsen ◽  
Karsten Bjerre ◽  
Anne E. Lykkesfeldt ◽  
Anita Giobbie-Hurder ◽  
Anne-Vibeke Lænkholm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Adjuvant Endocrine Therapy ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Predicting Outcome ◽  
Positive Breast Cancer

scholarly journals Identification of TACC1, NOV, and PTTG1 as new candidate genes associated with endocrine therapy resistance in breast cancer

2008 ◽  
Vol 42 (2) ◽  
pp. 87-103 ◽  
Author(s):  
Sandra E Ghayad ◽  
Julie A Vendrell ◽  
Ivan Bieche ◽  
Frédérique Spyratos ◽  
Charles Dumontet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Candidate Genes ◽  
Endocrine Therapy ◽  
Cell Lines ◽  
Tamoxifen Treatment ◽  
Cross Resistance ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

Cross-resistance to molecules used in endocrine therapy is among the main challenges in the treatment of estrogen receptor-α (ERα) positive breast cancer. In this study, we used two different cell models of resistance to anti-estrogens: MVLN/CL6.7 cells and VP229/VP267 cells selected after exposure to tamoxifen respectively in vitro and in vivo to characterize a phenotype rarely observed, i.e. acquisition of cross-resistance to the pure ER antagonist fulvestrant. As MVLN/CL6.7 cells and VP229/VP267 cell lines are original and valuable models of cross-resistance to tamoxifen and fulvestrant, we examined candidate genes using a RTQ-PCR strategy to identify new biomarkers of endocrine resistance. Out of the 26 candidate genes tested, 19 displayed deregulation of expression at the basal level in at least one of the two resistant cell lines. Eight genes (TACC1, NOV, PTTG1, MAD2L1, BAK1, TGFB2, BIRC5, and CCNE2) were significantly overexpressed in samples from ER-positive breast cancer patients who relapsed after tamoxifen treatment (n=24) compared with samples from patients who did not (n=24). Five genes (TACC1, NOV, PTTG1, BAK1, and TGFB2) were correlated with significantly shorter relapse-free survival (univariate analysis). Finally, we identified TACC1 and a three-gene expression signature (TACC1, NOV, and PTTG1) as independent prognostic markers (multivariate analysis). Aberrant mRNA and protein levels of TACC1, NOV, and PTTG1 were also observed under tamoxifen and/or fulvestrant exposure in resistant CL6.7 cells compared with their respective control MVLN cells. In conclusion, our data identify TACC1, NOV, and PTTG1 as promising new markers that could be used in the clinical management of ER-positive breast cancer patients.

Efficacy of six month neoadjuvant endocrine therapy in postmenopausal, hormone receptor-positive breast cancer patients – A phase II trial

2014 ◽  
Vol 50 (13) ◽  
pp. 2190-2200 ◽  
Author(s):  
Duveken B.Y. Fontein ◽  
Ayoub Charehbili ◽  
Johan W.R. Nortier ◽  
Elma Meershoek-Klein Kranenbarg ◽  
Judith R. Kroep ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Phase Ii ◽  
Hormone Receptor ◽  
Phase Ii Trial ◽  
Breast Cancer Patients ◽  
Neoadjuvant Endocrine Therapy ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer
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