scholarly journals Estrogen receptor α geneESR1amplification may predict endocrine therapy responsiveness in breast cancer patients

2009 ◽  
Vol 100 (6) ◽  
pp. 1012-1017 ◽  
Author(s):  
Saori Tomita ◽  
Zhenhuan Zhang ◽  
Masahiro Nakano ◽  
Mutsuko Ibusuki ◽  
Teru Kawazoe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Estrogen Receptor Α ◽  
Breast Cancer Patients

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 Phosphorylation of Estrogen Receptor-α at Ser167 Is Indicative of Longer Disease-Free and Overall Survival in Breast Cancer Patients

2007 ◽  
Vol 13 (19) ◽  
pp. 5769-5776 ◽  
Author(s):  
Jie Jiang ◽  
Naveed Sarwar ◽  
David Peston ◽  
Elena Kulinskaya ◽  
Sami Shousha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Estrogen Receptor Α ◽  
Breast Cancer Patients ◽  
Disease Free

scholarly journals Prolylcarboxypeptidase Promotes IGF1R/HER3 Signaling and Is a Potential Target to Improve Endocrine Therapy Response in Estrogen Receptor Positive Breast Cancer

2021 ◽  
Author(s):  
Lei Duan ◽  
Sarah J Calhoun ◽  
Ricardo E Perez ◽  
Virgilia Macias ◽  
Fatima Mir ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Breast Cancer Patients ◽  
Peptide Substrates ◽  
Rtk Signaling ◽  
Potential Target ◽  
Clinical Databases ◽  
Estrogen Receptor Positive

Abstract Background Prolylcarboxypeptidase (PRCP) is a lysosomal serine protease that cleaves peptide substrates when the penultimate amino acid is proline. Previous studies have linked PRCP to blood-pressure and appetite control through its ability to cleave peptide substrates such as angiotensin II and a-MSH. A potential role for PRCP in cancer has to date not been widely appreciated. Endocrine therapy resistance in breast cancer is an enduring clinical problem mediated in part by aberrant receptor tyrosine kinase (RTK) signaling. We previously found PRCP overexpression promoted tamoxifen (TAM) resistance in estrogen receptor-positive (ER+) breast cancer cells. Currently we tested the potential association between PRCP with breast cancer patient outcome and RTK signaling, and tumor responsiveness to endocrine therapy. Methods We analyzed PRCP protein expression by IHC staining of ER+ breast cancer samples and PRCP gene expression in clinical databases and used Kaplan-Meier survival curves to determine the significance of PRCP expression correlation with recurrence free survival and overall survival. We analyzed PRCP-regulated IGF1R/HER3 signaling using immunoblotting in the ER+ MCF7 cell line. We analyzed the therapeutic effect of a PRCP specific inhibitor (PRCPi) and/or endoxifen on tumor growth of ER+ PDX tumors and MCF7 tumors in immunocompromised mice. ResultsWe found high PRCP protein levels in tumors associates with worse outcome and earlier recurrence in breast cancer patients, including patients treated with TAM. Analyses of clinical databases showed that PRCP expression correlates with IGF1 and NRG1 expression and their target genes and earlier recurrence in endocrine-treated ER+/HER2- breast cancer patients. Overexpression of PRCP increased IGF1R/HER3 signaling. PRCPi blocked IGF1R/HER3 signaling and enhanced the response of ER+ breast cancer tumors in mice to endoxifen, the active metabolite of TAM. ConclusionsPRCP is an adverse prognostic marker in breast cancer and a potential target to improve endocrine therapy in ER+ breast cancers.

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