Using Expression Profiling to Understand the Effects of Chronic Cadmium Exposure on MCF-7 Breast Cancer Cells

Lubovac-Pilav, Zelmina; Borràs, Daniel; Ponce, Esmeralda; Louie, Maggie C.

doi:10.1371/journal.pone.0084646

Cited by 18 publications

(17 citation statements)

References 65 publications

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“…While our data suggest a positive correlation between cadmium exposure and the expression of these proteins, it is likely other ubiquitinationassociated proteins involved in the ubiquitination pathways are also affected by cadmium. In support of this, our recent microarray analysis identified multiple ubiquitination-associated genes deregulated in five different breast cancer clonal cell lines chronically exposed to cadmium (Table S1) [46]. The results from this study along with indications from the microarray analysis warrant further studies to examine the role of cadmium in protein stability.…”

Section: Discussionsupporting

confidence: 67%

“…Future research aimed at dissecting the role of ERα in cadmium‐induced E‐cadherin ubiquitination may offer further insights into how this heavy metal contributes to breast cancer progression. In addition, it would be worth investigating whether or not chronic cadmium exposure promotes epithelial mesenchymal transition (EMT), particularly in light of our recent microarray analysis study , which does indicate that multiple genes associated with EMT are deregulated in the presence of cadmium ().…”

Section: Discussionmentioning

confidence: 99%

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Acute and chronic cadmium exposure promotes E‐cadherin degradation in MCF7 breast cancer cells

Ponce

Louie

Sevigny

2014

Molecular Carcinogenesis

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Cadmium is an environmental carcinogen that usually enters the body at minute concentrations through diet or cigarette smoke and bioaccumulates in soft tissues. In past studies, cadmium has been shown to contribute to the development of more aggressive cancer phenotypes including increased cell migration and invasion. This study aims to determine if cadmium exposure-both acute and chronic-contributes to breast cancer progression by interfering with the normal functional relationship between E-cadherin and β-catenin. An MCF7 breast cancer cell line (MCF7-Cd) chronically exposed to 10(-7) M CdCl2 was previously developed and used as a model system to study chronic exposures, whereas parental MCF7 cells exposed to 10(-6) M CdCl2 for short periods of time were used to study acute exposures. Cadmium exposure of MCF7 cells led to the degradation of the E-cadherin protein via the ubiquitination pathway. This resulted in fewer E-cadherin/β-catenin complexes and the relocation of active β-catenin to the nucleus, where it interacted with transcription factor TCF-4 to modulate gene expression. Interestingly, only cells chronically exposed to cadmium showed a significant decrease in the localization of β-catenin to the plasma membrane and an increased distance between cells. Our data suggest that cadmium exposure promotes breast cancer progression by (1) down-regulating E-cadherin, thus decreasing the number of E-cadherin/β-catenin adhesion complexes, and (2) enhancing the nuclear translocation of β-catenin to increase expression of cancer-promoting proteins (i.e., c-Jun and cyclin D1).

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Acute and chronic cadmium exposure promotes E‐cadherin degradation in MCF7 breast cancer cells

Ponce

Louie

Sevigny

2014

Molecular Carcinogenesis

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“…Li et al ( 40 ) noted that PRSS30P is upregulated in lung adenocarcinoma. SCARNA9 is observed to be overexpressed in breast cancer cells on exposure to cadmium ( 41 ). However, ARHGAP5-AS1 and MCF2L-AS1 are rarely studied in cancer.…”

Section: Discussionmentioning

confidence: 99%

LASSO‑based Cox‑PH model identifies an 11‑lncRNA signature for prognosis prediction in gastric cancer

Zhang

et al. 2018

Mol Med Report

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The present study aimed to identify a long non-coding (lnc) RNAs-based signature for prognosis assessment in gastric cancer (GC) patients. By integrating gene expression data of GC and normal samples from the National Center for Biotechnology Information Gene Expression Omnibus, the EBI ArrayExpress and The Cancer Genome Atlas (TCGA) repositories, the common RNAs in Genomic Spatial Event (GSE) 65801, GSE29998, E-MTAB-1338, and TCGA set were screened and used to construct a weighted correlation network analysis (WGCNA) network for mining GC-related modules. Consensus differentially expressed RNAs (DERs) between GC and normal samples in the four datasets were screened using the MetaDE method. From the overlapped lncRNAs shared by preserved WGCNA modules and the consensus DERs, an lncRNAs signature was obtained using L1-penalized (lasso) Cox-proportional hazard (PH) model. LncRNA-mRNA networks were constructed for these signature lncRNAs, followed by functional annotation. A total of 14,824 common mRNAs and 2,869 common lncRNAs were identified in the 4 sets and 5 GC-associated WGCNA modules were preserved across all sets. MetaDE method identified 1,121 consensus DERs. A total of 50 lncRNAs were shared by preserved WGCNA modules and the consensus DERs. Subsequently, an 11-lncRNA signature was identified by LASSO-based Cox-PH model. The lncRNAs signature-based risk score could divide patients into 2 risk groups with significantly different overall survival and recurrence-free survival times. The predictive capability of this signature was verified in an independent set. These signature lncRNAs were implicated in several biological processes and pathways associated with the immune response, the inflammatory response and cell cycle control. The present study identified an 11-lncRNA signature that could predict the survival rate for GC.

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“…Because of the widespread use of cadmium, gastrointestinal absorption of cadmium without being aware is unavoidable. Several studies about carcinogenic effects of cadmium have been published and the cytotoxic action and carcinogenesis of cadmium in many organs, especially the lung, liver, breast, and kidney, are well known (16)(17)(18). However, the mechanisms underlying cadmium-induced carcinogenesis have remained largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Mukhin et al (26) suggested a simple model for ERK-1/2 activation by ROS (NAD(P)H oxidase → Giβγ → Src → ERK-1/2 pathway) using CHO cells. Concurrent inhibition of tyrosine phosphatase (PTPase) by ROS has been suggested to be another mechanism of ERK-1/2 activation (18). Because all PTPases have a conserved cysteine residue in their catalytic domain, the inhibition of PTPase activity by ROS may account for activation of ERK-1/2 by ROS.…”

Section: Discussionmentioning

confidence: 99%

Cadmium induces urokinase-type plasminogen activator receptor expression and the cell invasiveness of human gastric cancer cells via the ERK-1/2, NF-κB, and AP-1 signaling pathways

Khoi¹,

Xia²,

Lian³

et al. 2014

International Journal of Oncology

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Cadmium exposure has been linked to human cancers, including stomach cancer. In this study, the effects of cadmium on urokinase-type plasminogen activator receptor (uPAR) expression in human gastric cancer cells and the underlying signal transduction pathways were investigated. Cadmium induced uPAR expression in a time- and concentration-dependent manner. Cadmium also induced uPAR promoter activity. Additionally, cadmium induced the activation of extracellular signal regulated kinase-1/2 (ERK-1/2), p38 mitogen-activated protein kinase (MAPK), and the activation of c-Jun amino terminal kinase (JNK). A specific inhibitor of MEK-1 (PD98059) inhibited cadmium-induced uPAR expression, while JNK and p38 MAPK inhibitors did not. Expression vectors encoding dominant-negative MEK-1 (pMCL-K97M) also prevented cadmium-induced uPAR promoter activity. Site-directed mutagenesis and electrophoretic mobility shift studies showed that sites for the transcription factors nuclear factor (NF)-κB and activator protein-1 (AP-1) were involved in cadmium-induced uPAR transcription. Suppression of the cadmium-induced uPAR promoter activity by a mutated-type NF-κB-inducing kinase and I-κB and an AP-1 decoy oligonucleotide confirmed that the activation of NF-κB and AP-1 are essential for cadmium-induced uPAR upregulation. Cells pretreated with cadmium showed markedly enhanced invasiveness and this effect was partially abrogated by uPAR-neutralizing antibodies and by inhibitors of ERK-1/2, NF-κB, and AP-1. These results suggest that cadmium induces uPAR expression via ERK-1/2, NF-κB, and AP-1 signaling pathways and, in turn, stimulates cell invasiveness in human gastric cancer AGS cells.

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Using Expression Profiling to Understand the Effects of Chronic Cadmium Exposure on MCF-7 Breast Cancer Cells

Cited by 18 publications

References 65 publications

Acute and chronic cadmium exposure promotes E‐cadherin degradation in MCF7 breast cancer cells

Acute and chronic cadmium exposure promotes E‐cadherin degradation in MCF7 breast cancer cells

LASSO‑based Cox‑PH model identifies an 11‑lncRNA signature for prognosis prediction in gastric cancer

Cadmium induces urokinase-type plasminogen activator receptor expression and the cell invasiveness of human gastric cancer cells via the ERK-1/2, NF-κB, and AP-1 signaling pathways

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