Fluid Flow Stimulation Modulates Expression of S100 Genes in Normal Breast Epithelium and Breast Cancer

Abstract Introduction S100 proteins are intracellular calcium ion sensors that participate in cellular processes, some of which are involved in normal breast functioning and breast cancer development. Despite several S100 genes being overexpressed in breast cancer, their roles during disease development remain elusive. Human mammary epithelial cells (HMECs) can be exposed to fluid shear stresses and implications of such interactions have not been previously studied. The goal of this study was to analyze expression profiles of S100 genes upon exposing HMECs to fluid flow. Methods HMECs and breast cancer cell lines were exposed to fluid flow in a parallel-plate bioreactor system. Changes in gene expression were quantified using microarrays and qPCR, gene-gene interactions were elucidated using network analysis, and key modified genes were examined in three independent clinical datasets. Results S100 genes were among the most upregulated genes upon flow stimulation. Network analysis revealed interactions between upregulated transcripts, including interactions between S100P, S100PBP, S100A4, S100A7, S100A8 and S100A9. Overexpression of S100s was also observed in patients with early stage breast cancer compared to normal breast tissue, and in most breast cancer patients. Finally, survival analysis revealed reduced survival times for patients with elevated expression of S100A7 and S100P. Conclusion This study shows that exposing HMECs to fluid flow upregulates genes identified clinically to be overexpressed during breast cancer development, including S100A7 and S100P. These findings are the first to show that S100 genes are flow-responsive and might be participating in a fundamental adaptation pathway in normal tissue that is also active in breast cancer.

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

Cells ◽

10.3390/cells10040942 ◽

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.

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The oxytocin receptor signalling system and breast cancer: a critical review

Oncogene ◽

10.1038/s41388-020-01415-8 ◽

2020 ◽

Vol 39 (37) ◽

pp. 5917-5932 ◽

Cited By ~ 1

Author(s):

Huiping Liu ◽

Christian W. Gruber ◽

Paul F. Alewood ◽

Andreas Möller ◽

Markus Muttenthaler

Keyword(s):

Breast Cancer ◽

Current Knowledge ◽

Oxytocin Receptor ◽

Cancer Development ◽

Breast Cancer Cell Lines ◽

Maternal Behaviour ◽

Supporting Evidence ◽

Breast Cancer Development ◽

Signalling System ◽

Cancer Management

Abstract Breast cancer is making up one-quarter of all new female cancer cases diagnosed worldwide. Breast cancer surgeries, radiation therapies, cytotoxic chemotherapies and targeted therapies have made significant progress and play a dominant role in breast cancer patient management. However, many challenges remain, including resistance to systemic therapies, tumour recurrence and metastasis. The cyclic neuropeptide oxytocin (OT) elicits a plethora of biological responses via the oxytocin receptor (OTR) in both the central and peripheral nervous system, including social bonding, stress, maternal behaviour, sexual activity, uterus contraction, milk ejection and cancer. As a typical member of the G protein-coupled receptor family, OTR represents also an intriguing target for cancer therapy. There is emerging evidence that OTR plays a role in breast cancer development and progression, and several breast cancer cell lines express OTR. However, despite supporting evidence that OT lowers breast cancer risks, its mechanistic role in breast cancer development and the related signalling pathways are not fully understood. Here, we review the current knowledge of the OT/OTR signalling system in healthy breast tissue as well as in breast cancer, and discuss OTR as a potential therapeutic target for breast cancer management.

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Network Analysis of Gene Expression Profiles in Breast Cancer Cell Lines

Nutritional Genomics ◽

10.1201/b11294-17 ◽

2011 ◽

pp. 233-242

Author(s):

T Dewey ◽

Katie Streicher ◽

Stephen Ethier ◽

T Dewey ◽

Katie Streicher ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Network Analysis ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines

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ERK knockdown suppress cell biological activities via regulation CD59 in breast cancer

Archives of Medical Science ◽

10.5114/aoms/139683 ◽

2021 ◽

Author(s):

Fei Qu ◽

Yanru Cui ◽

Shixin Yang ◽

Zhihua Li ◽

Jingxian Ding ◽

...

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Biological Activities ◽

Cell Number ◽

Tunel Assay ◽

Cancer Development ◽

Breast Cancer Cell Lines ◽

Breast Cancer Development

IntroductionIt has been unclear that ERK play the effects and relative mechanism in breast cancer development. The purpose of this work was to discuss the ERK play the effect in breast cancer and relative mechanisms.Material and methodsEvaluating ERK and CD59 proteins expression in difference tissue from patients by IHC assay. Using MCF-7 and MDA-MB-231 cell lines which were breast cancer cell lines as target cell lines in our study. In vitro study, evaluating cell biological activities including proliferation, apoptosis, cell cycle, invasion, adherent and migration by MTT, clone test, TUNEL assay, flow cytometry and wound healing. And measuring relative proteins expressions by WB assay. In vivo study, measuring tumor weight and volume, the apoptosis cell number were evaluated by TUNEL assay and relative proteins expressions by IHC assay.ResultsCompared with adjacent normal tissue, the ERK and CD59 proteins expression were significantly increased in breast cancer tissues (P＜0.001, respectively).In vitro and vivo studies, with ERK knockdown, the cell biological activities were significantly depressed with CD59 suppressing (P＜0.001, respectively). And the relative proteins including CD59, PKD, P53, E-cadherin and Vimentin were significantly differences (P＜0.001, respectively).ConclusionsERK play an oncology gene in breast cancer development, ERK inhibitor had effects to suppress breast cancer biological via regulation CD59 in vitro and vivo study.

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