A Major Role of p95/611-CTF, a Carboxy-Terminal Fragment of HER2, in the Down-modulation of the Estrogen Receptor in HER2-Positive Breast Cancers

2010 ◽  
Vol 70 (21) ◽  
pp. 8537-8546 ◽  
Author(s):  
Josep Lluís Parra-Palau ◽  
Kim Pedersen ◽  
Vicente Peg ◽  
Maurizio Scaltriti ◽  
Pier Davide Angelini ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Terminal Fragment ◽  
Carboxy Terminal

scholarly journals Different mechanisms for resistance to trastuzumab versus lapatinib in HER2- positive breast cancers - role of estrogen receptor and HER2 reactivation

2011 ◽  
Vol 13 (6) ◽  
Author(s):  
Yen-Chao Wang ◽  
Gladys Morrison ◽  
Ryan Gillihan ◽  
Jun Guo ◽  
Robin M Ward ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Breast Cancers ◽  
Her2 Positive

scholarly journals Prognostic role of tumor size in T1 HER2-positive breast cancers treated with adjuvant trastuzumab

2014 ◽  
Vol 25 (5) ◽  
pp. 1073-1074 ◽  
Author(s):  
M. Campiglio ◽  
M. Sandri ◽  
M. Sasso ◽  
F. Bianchi ◽  
A. Balsari ◽  
...  
Keyword(s):  
Tumor Size ◽  
Breast Cancers ◽  
Prognostic Role ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab

scholarly journals miR-489 confines uncontrolled estrogen signaling through a negative feedback mechanism and regulates tamoxifen resistance in breast cancer

2020 ◽  
Author(s):  
Mithil Soni ◽  
Ozge Saatci ◽  
Yogin Patel ◽  
Manikanda Raja Keerthi Raja ◽  
Xinfeng Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Lines ◽  
Tamoxifen Resistance ◽  
Resistant Cell ◽  
Estrogen Signaling ◽  
Breast Cancers ◽  
Tamoxifen Resistant ◽  
Hormonal Therapies

Abstract Background Approximately 75% of diagnosed breast cancer tumors are Estrogen receptor (ER) positive tumors and are associated with better prognosis due to their response to hormonal therapies. However, around 40% of patients relapse after hormonal therapies. In the current study, we aimed to evaluate miR-489 as a novel molecular target to combat tamoxifen resistance.Methods Genomic analysis of gene expression profiles in primary breast cancers and tamoxifen resistant cell lines unveiled the potential role of miR-489 in regulation of estrogen signaling and development of tamoxifen resistance. We manipulated miR-489 expression in breast cancer cell lines by transient transfection of miR-489 mimic or establishment of knockout cell lines using the CRISPR/Cas9 system to study the reciprocal regulation of miR-489 and estrogen/ER signaling pathways. Cell proliferation, tumor sphere formation assay and flow cytometry analysis were conducted to investigate the role of miR-489 on estrogen-induced cell proliferation, cancer stem cells expansion and development of tamoxifen resistance.Results miR-489 expression was significantly downregulated in tamoxifen-resistant cell lines. Low levels of miR-489 were associated with poor clinical outcomes in patients with hormone treatment. In vitro analysis showed that loss of miR-489 expression promoted tamoxifen resistance while overexpression of miR-489 in tamoxifen-resistant cells restored tamoxifen sensitivity. Mechanistically, we found that miR-489 is an estrogen regulated miRNA that negatively regulated estrogen receptor signaling by using at least the following two mechanisms: i) modulation of ER phosphorylation status by inhibiting MAPK and AKT kinase activities; ii) regulation of nucleus to cytosol translocation of estrogen receptor α (ERα) by decreasing p38 expression and consequently ER phosphorylation. In addition, miR-489 could break the positive feed-forward loop between estrogen-ERα axis and p38 MAPK in breast cancer cells which was necessary for its function as transcription factor.Conclusion Our study unveiled the underlying molecular mechanism by which miR-489 regulates estrogen signaling pathway through a negative feedback loop and uncovered its role in the development of and overcoming tamoxifen resistance in breast cancers.

scholarly journals Circulating miRNAs in HER2-Positive and Triple Negative Breast Cancers: Potential Biomarkers and Therapeutic Targets

2020 ◽  
Vol 21 (18) ◽  
pp. 6750
Author(s):  
Ishita Gupta ◽  
Balsam Rizeq ◽  
Semir Vranic ◽  
Ala-Eddin Al Moustafa ◽  
Halema Al Farsi
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Triple Negative ◽  
Therapeutic Targets ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Circulating Mirnas ◽  
Her2 Positive ◽  
Cancer Disease ◽  
Estrogen Receptor Negative

Breast cancer is one of the most prevalent diseases among women worldwide and is highly associated with cancer-related mortality. Of the four major molecular subtypes, HER2-positive and triple-negative breast cancer (TNBC) comprise more than 30% of all breast cancers. While the HER2-positive subtype lacks estrogen and progesterone receptors and overexpresses HER2, the TNBC subtype lacks estrogen, progesterone and HER2 receptors. Although advances in molecular biology and genetics have substantially ameliorated breast cancer disease management, targeted therapies for the treatment of estrogen-receptor negative breast cancer patients are still restricted, particularly for TNBC. On the other hand, it has been demonstrated that microRNAs, miRNAs or small non-coding RNAs that regulate gene expression are involved in diverse biological processes, including carcinogenesis. Moreover, circulating miRNAs in serum/plasma are among the most promising diagnostic/therapeutic tools as they are stable and relatively easy to quantify. Various circulating miRNAs have been identified in several human cancers including specific breast cancer subtypes. This review aims to discuss the role of circulating miRNAs as potential diagnostic and prognostic biomarkers as well as therapeutic targets for estrogen-receptor negative breast cancers, HER2+ and triple negative.

scholarly journals Adjuvant application of trastuzumab in HER2 positive breast cancer and impact on time to relapse

2020 ◽  
Vol 26 (1) ◽  
pp. 10-15 ◽  
Author(s):  
Nikolina Dukic ◽  
Zdenka Gojkovic ◽  
Jelena Vladicic-Masic ◽  
Srdjan Masic ◽  
Nenad Lalovic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Human Monoclonal Antibody ◽  
Control Group ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Significant Difference ◽  
Time To Relapse ◽  
Positive Breast Cancer

Background: Of all breast cancers 20-25% are HER2 positive. Overexpression of HER2 protein on the surface of the malignant cell leads to excessive cell proliferation through different signaling pathways. Trastuzumab is a human monoclonal antibody that binds to domain IV of HER2 receptor and blocks signaling pathway for proliferation. The result is an improved prognosis for HER 2 positive breast cancer patients, even when compared to patients with other types of breast cancers. Methods: The study presents 74 women patients with early HER2 positive breast cancer who were previously operated (either radicaly or using breast conserving surgery), and received adjuvant chemo- and radiotherapy. Fourty four patients received adjuvant trastuzumab for one year, and 30 patients did not (control group). Observed time to relapse of the disease was 60 months. Results: There was a significant difference in survival in favor of the group that received trastuzumab (p<0.001). Application of trastuzumab also delayed relapse of the disease by 51.7%. No significant difference was observed between estrogen receptor positive and estrogen receptor negative cancers., In the control group there was a significant difference in relapse free survival in favor of estrogen and progesteron receptor positive tumors (p<0.001). Conclusion: Survival of patients with a HER2 positive breast cancer whose prognosis was initially worse compared to HER2 negative patients, significantly improved after administration of trastuzumab.

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