Potentials of CCL21 and CBS as therapeutic approaches for breast cancer

European Surgical Research ◽

10.1159/000521671 ◽

2022 ◽

Author(s):

Jing Peng ◽

Danhua Zhang

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Poor Prognosis ◽

Close Association ◽

Scratch Test ◽

Normal Breast ◽

Breast Epithelial Cell ◽

Epithelial Cell Line ◽

The Poor ◽

Breast Tissues

Objective: The present research set out to ascertain the roles of CCL21 and CBS in breast cancer (BC) cell biological behaviors and the relationship of CCL21 and CBS expression with the clinicopathological features of patients with BC. Methods: Immunohistochemistry of CCL21 or CBS was performed in 18 intraductal cancer tissues, 124 invasive BC tissues, 50 paraneoplastic tissues, 50 lobular hyperplasia tissues, and 30 normal breast tissues. For cell experiments, two human BC cell lines (MDA-MB-231 and MCF-7) and a human breast epithelial cell line (MCF-10A) were utilized to detect the expression of CCL21 and CBS. After loss- and gain-of-function assays for CCL21 or CBS, the expression of CBS and CCL21 was measured by qRT-PCR and Western blot. Additionally, BC cell proliferation was assessed by MTT assay and EdU staining, and BC cell migration was determined by scratch test and Transwell assay. Results: In the clinical data, the positive rate of CCL21 or CBS was significantly higher in invasive BC tissues than in intraductal BC tissues, lobular hyperplasia tissues, paraneoplastic tissues, and normal breast tissues (P < 0.05 or P < 0.01). CBS or CCL21 expression shared close association with the clinicopathological characteristic and the poor prognosis of BC patients. In cell experiments, overexpression of CCL21 or CBS enhanced the proliferative and migratory abilities of BC cells. Conclusion: CCL21 and CBS promoted BC cell migration and proliferation. CCL21 or CBS expression was strongly related to the poor prognosis of BC patients.

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Repression of protocadherin 17 is correlated with elevated angiogenesis and hypoxia markers in female patients with breast cancer

Cancer Biomarkers ◽

10.3233/cbm-201593 ◽

2021 ◽

pp. 1-10

Author(s):

Sanaa A. El-Benhawy ◽

Samia A. Ebeid ◽

Nadia A. Abd El Moneim ◽

Rabie R. Abdel Wahed ◽

Amal R.R. Arab

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Clinical Stage ◽

Suppressor Gene ◽

Normal Breast ◽

Vital Role ◽

Control Group ◽

Breast Cancer Patients ◽

Cd34 Cells ◽

Breast Tissues

BACKGROUND: Altered cadherin expression plays a vital role in tumorigenesis, angiogenesis and tumor progression. However, the function of protocadherin 17 (PCDH17) in breast cancer remains unclear. OBJECTIVE: Our target is to explore PCDH17 gene expression in breast carcinoma tissues and its relation to serum angiopoietin-2 (Ang-2), carbonic anhydrase IX (CAIX) and % of circulating CD34+ cells in breast cancer patients (BCPs). METHODS: This study included Fifty female BCPs and 50 healthy females as control group. Cancerous and neighboring normal breast tissues were collected from BCPs as well as blood samples at diagnosis PCDH17 gene expression was evaluated by RT-PCR. Serum Ang-2, CAIX levels were measured by ELISA and % CD34+ cells were assessed by flow cytometry. RESULTS: PCDH17 was downregulated in cancerous breast tissues and its repression was significantly correlated with advanced stage and larger tumor size. Low PCDH17 was significantly correlated with serum Ang-2, % CD34+ cells and serum CAIX levels. Serum CAIX, Ang-2 and % CD34+ cells levels were highly elevated in BCPs and significantly correlated with clinical stage. CONCLUSIONS: PCDH17 downregulation correlated significantly with increased angiogenic and hypoxia biomarkers. These results explore the role of PCDH17 as a tumor suppressor gene inhibiting tumor growth and proliferation.

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LncRNA GHET1 Promotes Hypoxia-Induced Glycolysis, Proliferation, and Invasion in Triple-Negative Breast Cancer Through the Hippo/YAP Signaling Pathway

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.643515 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yu Wang ◽

Shuwei Liu

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Nuclear Translocation ◽

Lactate Production ◽

Glucose Consumption ◽

Breast Epithelial Cell ◽

Epithelial Cell Line

ObjectiveThis study was to assess the specific impacts and mechanism of lncRNA GHET1 in the development of triple-negative breast cancer (TNBC).MethodsThe lncRNA GHET1 expression in TNBC tissues and adjacent healthy tissues was detected by qRT-PCR, and its expression was then measured at the cellular level, including TNBC cells and human normal breast epithelial cell line MCF10A. On the completion of transfection of negative shRNA or lncRNA GHET1 shRNA, the TNBC cells, HCC1937 and MDA-MB-468, were then cultured in a normoxia or hypoxia environment, respectively. 5-Ethynyl-2′-deoxyuridine (EdU) assay, colony formation assay, and transwell assay were applicable to the determination of cell proliferation, cell viability, and invasion in each group, respectively. Reagent kits were used for testing glucose consumption and lactate production levels. HCC1937 cells with knockdown or overexpression of lncRNA GHET1 were injected into the nude mice, followed by the examination of resulting tumor volume and weight. The distribution and expression of Hippo/YAP signaling pathway-related proteins were probed using western blotting.ResultsHighly expressed lncRNA GHET1 in TNBC tissues and cells and induction of lncRNA GHET1 by hypoxia were proved. Knockdown of lncRNA GHET1 significantly reduced proliferation, viability, and invasion of TNBC cells, and decreased glucose consumption and lactate production levels under the hypoxia condition. Furthermore, lncRNA GHET1 knockdown decreased HIF-1α expression in hypoxia and significantly inhibited tumor development in vivo. Knockdown of lncRNA GHET1 increased the phosphorylation levels of LATS1 and Yes-associated protein (YAP) to retain YAP within the cytoplasm, while the overexpression of lncRNA GHET1 or hypoxia promoted nuclear translocation of YAP and TNBC development.ConclusionLncRNA GHET1 expression can be induced by hypoxia, which leads to excessive activation of the Hippo/YAP signaling pathway, thus promoting TNBC progression.

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Effect of Wnt5a on drug resistance in estrogen receptor-positive breast cancer

10.21203/rs.3.rs-96339/v1 ◽

2020 ◽

Author(s):

Ai Amioka ◽

Takayuki Kadoya ◽

Satoshi Sueoka ◽

Yoshie Kobayashi ◽

Shinsuke Sasada ◽

...

Keyword(s):

Breast Cancer ◽

Poor Prognosis ◽

Breast Cancer Tissue ◽

Cancer Tissue ◽

Breast Cancer Patients ◽

Mtor Signaling Pathway ◽

The Poor ◽

Er Positive ◽

Mcf 7 ◽

Positive Breast Cancer

Abstract BackgroundIt was previously reported by us that Wnt5a-positive breast cancer can be classified as estrogen receptor (ER)-positive breast cancer and its prognosis is worse than that of Wnt5a-negative breast cancer. Herein, the molecular mechanisms underlying the poor prognosis of Wnt5a-positive breast cancer patients were examined. MethodsA total of 151 consecutive ER-positive breast cancer patients who underwent resection between January 2011 and February 2014 were enrolled. DNA microarray and pathway analyses were performed conducted using MCF-7 cells stably expressing Wnt5a (MCF-7/Wnt5a(+)). Based on the results, cell viability and drug sensitivity assays as well as mutation analysis , were performed using culture cells and breast cancer tissue. The relationship between Wnt5a and the PI3K–AKT–mTOR signaling pathway was examined.ResultsThe relapse-free survival rate in patients with Wnt5a-positive breast cancer was significantly lower than that in patients with Wnt5a-negative breast cancer ( P = 0.047). DNA microarray data indicated that only the cytochrome P450 (CYP) pathway was significantly upregulated in MCF-7/Wnt5a(+) cells ( P = 0.0440). MCF-7/Wnt5a(+) cells showed reduced sensitivity to the metabolic substrates of CYP, tamoxifen ( P < 0.001), and paclitaxel ( P < 0.001). PIK3CA mutations were unrelated to Wnt5a expression in breast cancer tissue and culture cells.ConclusionsIn ER-positive breast cancer, Wnt5a upregulated the CYP metabolic pathway; additionally, it inhibited the sensitivity to tamoxifen and paclitaxel, which constitute the standard treatment options for ER-positive breast cancer. Wnt5a could be involved in the poor prognosis of ER-positive breast cancer independently of the PI3K–AKT–mTOR signaling pathway.

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Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis

Bioscience Reports ◽

10.1042/bsr20191764 ◽

2020 ◽

Vol 40 (4) ◽

Cited By ~ 1

Author(s):

Chong Lu ◽

Xiuhua Wang ◽

Xiangwang Zhao ◽

Yue Xin ◽

Chunping Liu

Keyword(s):

Breast Cancer ◽

Normal Breast ◽

Tumor Promoter ◽

Women Health ◽

Non Coding Rna ◽

Non Coding Rnas ◽

And Migration ◽

Breast Tissues ◽

Long Non Coding Rna

Abstract Breast cancer (BC) poses a great threaten to women health. Numerous evidences suggest the important role of long non-coding RNAs (lncRNAs) in BC development. In the present study, we intended to investigate the role of ARAP1-AS1 in BC progression. First of all, the GEPIA data suggested that ARAP1-AS1 was highly expressed in breast invasive carcinoma (BRAC) tissues compared with the normal breast tissues. Meanwhile, the expression of ARAP1-AS1 was greatly up-regulated in BC cell lines. ARAP1-AS1 knockdown led to repressed proliferation, strengthened apoptosis and blocked migration of BC cells. Moreover, ARAP1-AS1 could boost HDAC2 expression in BC through sponging miR-2110 via a ceRNA mechanism. Of note, the UCSC predicted that HDAC2 was a potential transcriptional regulator of PLIN1, an identified tumor suppressor in BC progression. Moreover, we explained that the repression of HDAC2 on PLIN1 was owing to its deacetylation on PLIN1 promoter. More importantly, depletion of PLIN1 attenuated the mitigation function of ARAP1-AS1 silence on the malignant phenotypes of BC cells. To sum up, ARAP1-AS1 serves a tumor-promoter in BC development through modulating miR-2110/HDAC2/PLIN1 axis, which may help to develop novel effective targets for BC treatment.

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FGF12 is differentially expressed in the brain metastases of patients with metastatic breast cancer.

10.31219/osf.io/7e5wd ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Brain Metastases ◽

Metastatic Breast ◽

Metastatic Tumor ◽

Clinical Problem ◽

Normal Breast ◽

Primary Tumors ◽

Breast Tissues ◽

The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that the fibroblast growth factor 12, encoded by FGF12, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to normal breast tissues. FGF12 mRNA expression was significantly higher in brain metastatic tissues as compared to primary tumors of the breast. Up-regulation of FGF12 expression may contribute to metastasis of tumor cells from the breast to the brain in humans with metastatic breast cancer.

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C1R is differentially expressed in the brain metastases of patients with metastatic breast cancer.

10.31219/osf.io/p9eyr ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Brain Metastases ◽

Metastatic Breast ◽

Metastatic Tumor ◽

Clinical Problem ◽

Normal Breast ◽

Primary Tumors ◽

Breast Tissues ◽

The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that the complement component 1, r subcomponent, encoded by C1R, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to normal breast tissues. C1R mRNA was present at significantly reduced quantities in brain metastatic tissues as compared to primary tumors of the breast. Down-regulation of C1R expression may contribute to metastasis of tumor cells from the breast to the brain in humans with metastatic breast cancer.

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Promoter Methylation Status of the Retinoic Acid Receptor-Beta 2 Gene in Breast Cancer Patients: A Case Control Study and Systematic Review

Breast Care ◽

10.1159/000489874 ◽

2019 ◽

Vol 14 (2) ◽

pp. 117-123 ◽

Cited By ~ 1

Author(s):

Kheirollah Yari ◽

Zohreh Rahimi

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Retinoic Acid Receptor ◽

Methylation Status ◽

Normal Breast ◽

Breast Cancer Patients ◽

Retinoic Acid Receptor Beta ◽

Cancer Tissues ◽

Breast Tissues ◽

Receptor Beta

Background: We aimed to determine the promoter methylation status of the retinoic acid receptor-beta 2 (RARβ2) gene among breast cancer patients and to review relevant studies in this field in various populations. Methods: We analyzed 400 samples which comprised blood specimens from 102 breast cancer patients, 102 first-degree female relatives of patients, 100 cancer-free females, 48 breast cancer tissues, and 48 adjacent normal breast tissues from the same patients. The RARβ2 methylation status was determined using methylation-specific polymerase chain reaction (MSP) and DNA sequencing methods. Results: The presence of combined partially methylated (MU) and fully methylated (MM) forms of the RARβ2 gene (MU+MM) in the blood of patients was associated with susceptibility to breast cancer (odds ratio = 4.7, p = 0.05). A significantly higher frequency of the MM genotype was observed in cancer tissue (10.4%) compared to matched adjacent normal breast tissue (0%) (p = 0.02). Conclusion: We found a higher frequency of RARβ2 gene methylation in the blood and cancer tissues of patients compared to the blood of controls and adjacent normal breast tissues. The survey of studies on various populations demonstrated a higher RARβ2 methylation frequency in breast cancer patients compared to normal individuals, and many reports suggest a significant association between hypermethylation of the gene and susceptibility to breast cancer.

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Promoter Hypermethylation and Suppression of Glutathione Peroxidase 3 Are Associated with Inflammatory Breast Carcinogenesis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2014/787195 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 22

Author(s):

Mona M. Mohamed ◽

Salwa Sabet ◽

Dun-Fa Peng ◽

M. Akram Nouh ◽

Mohamed El-Shinawi ◽

...

Keyword(s):

Breast Cancer ◽

Glutathione Peroxidase ◽

Cancer Progression ◽

Epigenetic Regulation ◽

Ductal Carcinoma ◽

Methylation Status ◽

Promoter Hypermethylation ◽

Normal Breast ◽

Glutathione Peroxidase 3 ◽

Breast Tissues

Reactive oxygen species (ROS) play a crucial role in breast cancer initiation, promotion, and progression. Inhibition of antioxidant enzymes that remove ROS was found to accelerate cancer growth. Studies showed that inhibition of glutathione peroxidase-3 (GPX3) was associated with cancer progression. Although the role of GPX3 has been studied in different cancer types, its role in breast cancer and its epigenetic regulation have not yet been investigated. The aim of the present study was to investigate GPX3 expression and epigenetic regulation in carcinoma tissues of breast cancer patients’ in comparison to normal breast tissues. Furthermore, we compared GPX3 level of expression and methylation status in aggressive phenotype inflammatory breast cancer (IBC) versus non-IBC invasive ductal carcinoma (IDC). We found that GPX3 mRNA and protein expression levels were downregulated in the carcinoma tissues of IBC compared to non-IBC. However, we did not detect significant correlation between GPX3 and patients’ clinical-pathological prosperities. Promoter hypermethylation of GPX3 gene was detected in carcinoma tissues not normal breast tissues. In addition, IBC carcinoma tissues showed a significant increase in the promoter hypermethylation of GPX3 gene compared to non-IBC. Our results propose that downregulation of GPX3 in IBC may play a role in the disease progression.

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