scholarly journals Novel Stromal Biomarkers in Human Breast Cancer Tissues Provide Evidence for the More Malignant Phenotype of Estrogen Receptor-Negative Tumors

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Zahraa I. Khamis ◽  
Ziad J. Sahab ◽  
Stephen W. Byers ◽  
Qing-Xiang Amy Sang
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Human Breast Cancer ◽  
Genetic Alterations ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Human Breast Carcinomas ◽  
Er Positive ◽  
Cancer Tissues

Research efforts were focused on genetic alterations in epithelial cancer cells. Epithelial-stromal interactions play a crucial role in cancer initiation, progression, invasion, angiogenesis, and metastasis; however, the active role of stroma in human breast tumorigenesis in relation to estrogen receptor (ER) status of epithelial cells has not been explored. Using proteomics and biochemical approaches, we identified two stromal proteins in ER-positive and ER-negative human breast cancer tissues that may affect malignant transformation in breast cancer. Two putative biomarkers, T-cell receptor alpha (TCR-α) and zinc finger and BRCA1-interacting protein with a KRAB domain (ZBRK1), were detected in leukocytes of ER-positive and endothelial cells of ER-negative tissues, respectively. Our data suggest an immunosuppressive role of leukocytes in invasive breast tumors, propose a multifunctional nature of ZBRK1 in estrogen receptor regulation and angiogenesis, and demonstrate the aggressiveness of ER-negative human breast carcinomas. This research project may identify new stromal drug targets for the treatment of breast cancer patients.

A novel therapeutic strategy for ER-negative human breast cancers, targeting AP-1 activity

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14129-14129
Author(s):  
K. Sakaguchi ◽  
H. Nakajima ◽  
I. Fujiwara ◽  
N. Mizuta ◽  
J. Magae
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Human Breast Cancer Cell ◽  
Breast Cancers ◽  
Human Breast ◽  
Er Positive

14129 Background: While agents targeting estrogen receptors are the most effective in adjuvant therapy for human breast cancers expressing estrogen receptor(ER), breast cancers lacking ER are clinically serious, because they are highly malignant and exhibit resistance to the usual anti-cancer drugs, including estrogen receptor-antagonists and DNA breaking agents. Although a transcription factor, AP-1, is known to be related to tumor malignancy including metastasis, invasion and drug-resistance, it remains to be elucidated how AP-1 plays in development and expression of malignant characters of human breast cancers. Methods and Results: Here, we used MX-1, a human breast cancer cell line lacking ER and several ER positive cell lines, to clarify the roles of AP-1 and the therapeutic efficacy of ascochlorin, a newly developed prenylphenol antibiotic on ER-negative breast cancer. We found that MX-1 exhibited higher AP-1 activity and expressed higher levels of c-Jun, c-Fos and Fra-1 when compared with conventional ER-positive human breast cancer cell lines. Consistent with this study in vitro, histological study on human breast cancer tissues suggests that ER-negative cancers express high Fra-1 protein, and that paclitaxel- sensitive cancers express low Fra-1 protein. The ascochlorin, which inhibits AP-1 through the Erk signaling pathway, suppressed the AP-1 activity of MX-1 cells, and selectively killed MX-1 cells, partly due to induction of apoptosis. Moreover, administration of ascochlorin elongated life span of mice intraperitoneally implanted with murine mammary carcinoma cells. Conclusions: Our results suggest that AP-1 is an effective clinical target molecule for the treatment of ER-negative human breast cancer, and that ascochlorin is promising therapeutic agent for these refractory breast cancers. No significant financial relationships to disclose.

scholarly journals MiR-410 Acts as a Tumor Suppressor in Estrogen Receptor-Positive Breast Cancer Cells by Directly Targeting ERLIN2 via the ERS Pathway

2018 ◽  
Vol 48 (2) ◽  
pp. 461-474 ◽  
Author(s):  
Hewen Wu ◽  
Junli Li ◽  
En’en Guo ◽  
Suxia Luo ◽  
Guohui Wang
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Endoplasmic Reticulum ◽  
Estrogen Receptor ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Human Breast ◽  
Er Positive ◽  
Positive Breast Cancer

Background/Aims: Endoplasmic reticulum lipid raft-associated 2 (ERLIN2) is reported to be overexpressed in human breast cancer cells and plays an important role in cell proliferation. MicroRNAs (miRNAs) act as post-transcriptional regulators of gene expression and are involved in the development of multiple malignancies, including breast cancer. However, the molecular mechanism of the aberrant ERLIN2 expression in human breast cancer remains poorly understood. Methods: MiR-410 expression level was analyzed using Real-time PCR, and ERLIN2 expression was analyzed using Western blot, Real-time PCR and immunohistochemical staining. The effect of miR-410 on ERLIN2 3’UTR intensity was performed using a luciferase assay. Cell proliferation was analyzed using CCK-8 and colony formation assay, together with an Annexin V-PE/7-AAD kit for cell apoptosis assay. Cell migration and invasion was detected using a Transwell migration and invasion assay. Methylation specific PCR was used to examine whether miR-410 promoter was demethylated. Results: In this study, we validated that ERLIN2 was a direct target of miR-410 and miR-410 suppressed ERLIN2 expression at the post-transcriptional level. Importantly, the regulation of ERLIN2 by miR-410 was estrogen receptor (ER) dependent. Functional studies demonstrated that miR-410 inhibited breast cancer cell proliferation, migration and invasion, but promoted cell apoptosis. However, inhibition of miR-410 resulted in opposite effects. A xenograft nude mouse model further confirmed that miR-410 suppressed breast tumor growth. In addition, miR-410 modulated the expression levels of epithelial-mesenchymal transition (EMT)-related genes. ERLIN2 knockdown suppressed cell proliferation, migration and invasion, as well as EMT. ERLIN2 overexpression can restore the cell proliferation, migration and invasion that were inhibited by miR-410. Furthermore, our data demonstrated that miR-410 inhibition suppressed the expression of endoplasmic reticulum-stress (ERS)-related genes, while ERLIN2 knockdown abrogated the effects of miR-410 inhibitor. Finally, we showed that miR-410 was downregulated in human ER-positive breast cancer tissues, inversely correlated with ERLIN2. We further demonstrated the downregulation of miR-410 in breast cancer might be due to the hypermethylation of its promoter. Conclusions: Our study indicates that miR-410 suppresses cell growth, migration and invasion by directly downregulating ERLIN2 in ER positive breast cancer, acting as a tumor suppressor. Our study also suggests that miR-410 may serve as a potential therapeutic target for patients with ER positive breast cancer.

scholarly journals Transition into inflammatory cancer-associated adipocytes in breast cancer microenvironment requires microRNA regulatory mechanism

2016 ◽  
Author(s):  
Jiwoo Lee ◽  
Han Suk Ryu ◽  
Bok Sil Hong ◽  
Han-Byoel Lee ◽  
Minju Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Regulatory Mechanism ◽  
Luciferase Reporter ◽  
Cancer Microenvironment ◽  
Human Breast ◽  
Cancer Tissues

ABSTRACTSIntroductionThe role of adipocytes in cancer microenvironment has gained focus during the recent years. However, the characteristics of the cancer-associated adipocytes (CAA) in human breast cancer tissues and the underlying regulatory mechanism are not clearly understood.MethodWe reviewed pathology specimens of breast cancer patients to understand the morphologic characteristics of CAA, and profiled the mRNA and miRNA expression of CAA by using indirect co-culture system in vitro.ResultsThe CAAs in human breast cancers showed heterogeneous topographic relationship with breast cancer cells within the breast microenvironment. The CAAs exhibited the characteristics of de-differentiation determined by their microscopic appearance and the expression levels of adipogenic markers. Additionally, the 3T3-L1 adipocytes co-cultured with breast cancer cells showed up-regulation of inflammation-related genes including Il6 and Ptx3. The up-regulation of IL6 in CAA was further observed in human breast cancer tissues. miRNA array of co-cultured 3T3-L1 cells showed increased expression of mmu-miR-5112 which may target Cpeb1. Cpeb1 is a negative regulator of Il6. The suppressive role of mmu-miR-5112 was confirmed by dual luciferase reporter assay, and mmu-miR-5112-treated adipocytes showed up-regulation of Il6. The transition of adipocytes into more inflammatory CAA resulted in proliferation-promoting effect in ER positive breast cancer cells such as MCF7 and ZR-75-1 but not in ER negative cells.ConclusionIn this study, we have determined the de-differentiated and inflammatory natures of CAA in breast cancer microenvironment. Additionally, we propose a miRNA-based regulatory mechanism underlying the process of acquiring inflammatory phenotypes in CAA.

Expression of estrogen receptor beta isoforms in human breast cancer tissues and cell lines

2002 ◽  
Vol 71 (3) ◽  
pp. 249-255 ◽  
Author(s):  
Dan Tong ◽  
Eva Schuster ◽  
Michael Seifert ◽  
Klaus Czerwenka ◽  
Sepp Leodolter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Estrogen Receptor Beta ◽  
Human Breast ◽  
Cancer Tissues ◽  
Receptor Beta
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