scholarly journals Down-Regulation of the Proteoglycan Decorin Fills in the Tumor-Promoting Phenotype of Ionizing Radiation-Induced Senescent Human Breast Stromal Fibroblasts

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1987
Author(s):  
Eleni Mavrogonatou ◽  
Adamantia Papadopoulou ◽  
Asimina Fotopoulou ◽  
Stathis Tsimelis ◽  
Heba Bassiony ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ionizing Radiation ◽  
Cancer Progression ◽  
Breast Cancer Cell Lines ◽  
Phenotypic Trait ◽  
Mrna Levels ◽  
Human Breast ◽  
Down Regulation ◽  
Stromal Fibroblasts ◽  
Poor Prognostic Factor

Down-regulation of the small leucine-rich proteoglycan decorin in the stroma is considered a poor prognostic factor for breast cancer progression. Ionizing radiation, an established treatment for breast cancer, provokes the premature senescence of the adjacent to the tumor stromal fibroblasts. Here, we showed that senescent human breast stromal fibroblasts are characterized by the down-regulation of decorin at the mRNA and protein level, as well as by its decreased deposition in the pericellular extracellular matrix in vitro. Senescence-associated decorin down-regulation is a long-lasting process rather than an immediate response to γ-irradiation. Growth factors were demonstrated to participate in an autocrine manner in decorin down-regulation, with bFGF and VEGF being the critical mediators of the phenomenon. Autophagy inhibition by chloroquine reduced decorin mRNA levels, while autophagy activation using the mTOR inhibitor rapamycin enhanced decorin transcription. Interestingly, the secretome from a series of both untreated and irradiated human breast cancer cell lines with different molecular profiles inhibited decorin expression in young and senescent stromal fibroblasts, which was annulled by SU5402, a bFGF and VEGF inhibitor. The novel phenotypic trait of senescent human breast stromal fibroblasts revealed here is added to their already described cancer-promoting role via the formation of a tumor-permissive environment.

PRPS1 silencing reverses cisplatin resistance in human breast cancer cells

2017 ◽  
Vol 95 (3) ◽  
pp. 385-393 ◽  
Author(s):  
Min He ◽  
Lin Chao ◽  
Yi-Ping You
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Xenograft Model ◽  
Building Blocks ◽  
Nucleotide Metabolism ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Down Regulation ◽  
Nucleotide Synthesis

PRPS1 (phosphoribosyl pyrophosphate synthetase 1), which drives the nucleotide biosynthesis pathway, modulates a variety of functions by providing central building blocks and cofactors for cell homeostasis. As tumor cells often display abnormal nucleotide metabolism, dysregulated de-novo nucleotide synthesis has potential impacts in cancers. We now report that PRPS1 is specifically and highly expressed in chemoresistant (CR) cancer cells derived from cisplatin-resistant human breast cancer cell lines SK-BR-3 and MCF-7. The inhibition of PRPS1 activity in CR cells by genetic silencing reduces cell viability and increases apoptosis in vitro, both of which can be further potentiated by cisplatin treatment. Significantly, such down-regulation of PRPS1 in CR cells when administered to nude mice enhanced the survival of those animals, as demonstrated by decreased tumor growth. Knockdown of PRPSI may cause these effects by potently inducing autonomous activation of caspase-3 and inhibiting the proliferation in the engrafted CR tumors. As a result, cisplatin sensitivity in a xenograft model of CR cancer cells can be restored by the down-regulation of PRPS1. Thus, PRPS1 inhibition may afford a therapeutic approach to relapsed patients with breast cancer, resistant to chemotherapy.

scholarly journals Expression and Function of C1orf132 Long-Noncoding RNA in Breast Cancer Cell Lines and Tissues

2021 ◽  
Vol 22 (13) ◽  
pp. 6768
Author(s):  
Afsaneh Malekzadeh Shafaroudi ◽  
Ali Sharifi-Zarchi ◽  
Saeid Rahmani ◽  
Nahid Nafissi ◽  
Seyed Javad Mowla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Breast Cancer Cell Lines ◽  
Mcf7 Cells ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Migration Assay ◽  
And Function ◽  
Distal Promoter

miR-29b2 and miR-29c play a suppressive role in breast cancer progression. C1orf132 (also named MIR29B2CHG) is the host gene for generating both microRNAs. However, the region also expresses longer transcripts with unknown functions. We employed bioinformatics and experimental approaches to decipher C1orf132 expression and function in breast cancer tissues. We also used the CRISPR/Cas9 technique to excise a predicted C1orf132 distal promoter and followed the behavior of the edited cells by real-time PCR, flow cytometry, migration assay, and RNA-seq techniques. We observed that C1orf132 long transcript is significantly downregulated in triple-negative breast cancer. We also identified a promoter for the longer transcripts of C1orf132 whose functionality was demonstrated by transfecting MCF7 cells with a C1orf132 promoter-GFP construct. Knocking-out the promoter by means of CRISPR/Cas9 revealed no alterations in the expression of the neighboring genes CD46 and CD34, while the expression of miR-29c was reduced by half. Furthermore, the promoter knockout elevated the migration ability of the edited cells. RNA sequencing revealed many up- and downregulated genes involved in various cellular pathways, including epithelial to mesenchymal transition and mammary gland development pathways. Altogether, we are reporting here the existence of an additional/distal promoter with an enhancer effect on miR-29 generation and an inhibitory effect on cell migration.

scholarly journals Productive Infection of Human Breast Cancer Cell Lines with Human Cytomegalovirus (HCMV)

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 641
Author(s):  
Kaitlin M. Branch ◽  
Erica C. Garcia ◽  
Yin Maggie Chen ◽  
Matthew McGregor ◽  
Mikayla Min ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Tumor ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Breast Tumor Cells

Breast cancer is the leading cause of cancer deaths among women worldwide. There are many known risk factors for breast cancer, but the role of infectious disease remains unclear. Human cytomegalovirus (HCMV) is a widespread herpesvirus that usually causes little disease. Because HCMV has been detected in breast tumor biopsy samples and is frequently transmitted via human breast milk, we investigated HCMV replication in breast tumor cells. Four human breast cancer cell lines with different expression profiles for the key diagnostic markers of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were infected with a bacterial artificial chromosome-derived HCMV clinical strain TB40/E tagged with green fluorescent protein (GFP). Fluorescence microscopy confirmed that all four breast cancer cell lines supported virus entry. RNA was isolated from infected cells and the expression of immediate early (UL123), early (UL54), and late (UL111A) genes was confirmed using PCR. Viral proteins were detected by immunoblotting, and viral progeny were produced during the infection of breast tumor cells, as evidenced by subsequent infection of fibroblasts with culture supernatants. These results demonstrate that breast tumor cells support productive HCMV infection and could indicate that HCMV replication may play a role in breast cancer progression.

scholarly journals MRCKα Is Dispensable for Breast Cancer Development in the MMTV-PyMT Model

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 942
Author(s):  
Mei Qi Kwa ◽  
Rafael Brandao ◽  
Trong H. Phung ◽  
Jianfeng Ge ◽  
Giuseppe Scieri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression Signature ◽  
Genomic Analysis ◽  
Cancer Development ◽  
Breast Cancer Cell Lines ◽  
Normal Mammary Gland ◽  
Breast Cancers ◽  
Human Breast ◽  
Breast Cancer Development

MRCKα is a ubiquitously expressed serine/threonine kinase involved in cell contraction and F-actin turnover, which is highly amplified in human breast cancer and part of a gene expression signature for bad prognosis. Nothing is known about the in vivo function of MRCKα. To explore MRCKα function in development and in breast cancer, we generated mice lacking a functional MRCKα gene. Mice were born close to the Mendelian ratio and showed no obvious phenotype including a normal mammary gland formation. Assessing breast cancer development using the transgenic MMTV-PyMT mouse model, loss of MRCKα did not affect tumor onset, tumor growth and metastasis formation. Deleting MRCKα and its related family member MRCKβ in two triple-negative breast cancer cell lines resulted in reduced invasion of MDA-MB-231 cells, but did not affect migration of 4T1 cells. Further genomic analysis of human breast cancers revealed that MRCKα is frequently co-amplified with the oncogenes ARID4B and AKT3 which might contribute to the prognostic value of MRCKα expression. Collectively, these data suggest that MRCKα might be a prognostic marker for breast cancer, but probably of limited functional importance.

scholarly journals Stromal CCL5 Promotes Breast Cancer Progression by Interacting with CCR3 in Tumor Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 1918
Author(s):  
Mio Yamaguchi ◽  
Kiyoshi Takagi ◽  
Koki Narita ◽  
Yasuhiro Miki ◽  
Yoshiaki Onodera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Human Breast Carcinoma ◽  
Breast Cancer Patients ◽  
Breast Carcinomas ◽  
Human Breast

Chemokines secreted from stromal cells have important roles for interactions with carcinoma cells and regulating tumor progression. C-C motif chemokine ligand (CCL) 5 is expressed in various types of stromal cells and associated with tumor progression, interacting with C-C chemokine receptor (CCR) 1, 3 and 5 expressed in tumor cells. However, the expression on CCL5 and its receptors have so far not been well-examined in human breast carcinoma tissues. We therefore immunolocalized CCL5, as well as CCR1, 3 and 5, in 111 human breast carcinoma tissues and correlated them with clinicopathological characteristics. Stromal CCL5 immunoreactivity was significantly correlated with the aggressive phenotype of breast carcinomas. Importantly, this tendency was observed especially in the CCR3-positive group. Furthermore, the risk of recurrence was significantly higher in the patients with breast carcinomas positive for CCL5 and CCR3 but negative for CCR1 and CCR5, as compared with other patients. In summary, the CCL5-CCR3 axis might contribute to a worse prognosis in breast cancer patients, and these findings will contribute to a better understanding of the significance of the CCL5/CCRs axis in breast carcinoma microenvironment.

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