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.

Comparing outcomes of neoadjuvant endocrine therapy versus chemotherapy in ER-positive breast cancer: Results from a prospective institutional database.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 581-581 ◽  
Author(s):  
Nathalie LeVasseur ◽  
Walter Yip ◽  
Huaqi Li ◽  
Kaylie Willems ◽  
Caroline Illmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Clinical Stage ◽  
Breast Cancer Patients ◽  
Long Term Outcomes ◽  
Neoadjuvant Endocrine Therapy ◽  
Er Positive ◽  
Positive Breast Cancer

581 Background: While neoadjuvant chemotherapy (NACT) has been established as the standard of care for medically fit patients, there has been renewed interest in utilizing neoadjuvant endocrine therapy (NET) for the treatment of women with estrogen-receptor (ER) positive, HER-2 negative breast cancer. Rates of pCR are known to be low in this population, but there is inconsistent data regarding downstaging and long-term outcomes in a non-trial setting with NET vs NACT. Methods: A prospective institutional databaseof breast cancer patients treated with neoadjuvant therapy at the British Columbia Cancer Agency from 2012-2016 was analyzed to identify all medically fit patients with ER positive, HER2 negative breast cancer. Patients were then divided into two groups: those who received NET or NACT. Baseline characteristics were compared between groups. A matched analysis (age, stage and grade) was then performed to compare rates of downstaging, pCR and scores from a validated neoadjuvant therapy outcomes calculator (CPS+EG). Results: A total of 154 patients met eligibility criteria for this study. One hundred and six patients (69%) received NACT and 48 (31%) received NET. Women offered NACT were significantly younger (51 vs 64y, p < 0.001) than those offered endocrine therapy and presented with a higher clinical stage (LR 27.93, p = 0.002). According to multiple linear regression for downstaging, clinical stage followed by NACT were the most important predictors of downstaging. When matched for age, stage and grade, downstaging was significantly higher with NACT (31/48, 65%) as compared to NET (12/48, 25%), p < 0.001. Of these, 12.5% achieved pCR with NACT as compared to 2.1% with NET, LR 4.243, p = 0.039. No significant differences in CPS+EG scores were identified when comparing NACT to NET. Conclusions: Significantly higher rates of downstaging were achieved with NACT as compared to NET when patients were matched for age, stage and grade. Rates of pCR remain low for ER-positive breast cancer patients. Although not validated with the use of NET, CPS+EG scores predicting long-term outcomes were not significantly different with NET compared to NACT.

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