Biomedical Sciences Research Seminar

System biology study of metformin molecular mechanism in breast cancer

Atomic structure of a biological molecule
Seminars

As part of the School of Science and Technology Biomedical Sciences Research Centre Seminar Series, Shaymaa Al-Juboori, NTU presents: System biology study of metformin molecular mechanism in breast cancer.

  • From: Wednesday 17 October 2018, 1 pm
  • To: Wednesday 17 October 2018, 2 pm
  • Location: 282, Erasmus Darwin, Nottingham Trent University, Clifton Campus, Clifton Lane, Nottingham, NG11 8NS

Past event

Event details

As part of the School of Science and Technology Biomedical Sciences Research Centre Seminar Series, Shaymaa Al-Juboori, NTU presents: System biology study of metformin molecular mechanism in breast cancer.

Abstract

Globally, breast cancer represents the most common cause of cancer death among women, with an incidence of 12% females developing invasive breast cancer during their lifetime. It is a complicated multifaceted heterogeneous disease, which shows a wide spectrum of structures that demonstrates diversity of clinical, morphological and molecular features. As a consequent of this variation diverse response patterns appeared in response to different treatments regimes.
The anti-diabetic drug Metformin has been commonly prescribed to treat type 2 diabetes patients since 1957 with well-established side effect and safety profile. Additionally, cancer researchers have studied the anti-tumour effects of this drug since 2005, after the first report, which associated metformin usage with a reduction in cancer incidence. Thus, Metformin has suggested as an ideal candidate to treat and prevent different types of cancers, including breast carcinoma.
This study was designed to interrogate metformin mode of action in different subtypes of breast cancer by utilising cell biology, molecular biology, and system biology techniques. To that end, several dosages of metformin have been used on different breast cancer cell lines accordingly to breast cancer divergence. Interestingly, treatments with metformin induced the same response model in all cell lines and at different concentrations. However, slight differences were observed between the different cell lines. Metformin treatment significantly reduced the cell viability, number of cells and proliferating of cells while induced cell apoptosis and enhanced cell necrosis of the Basal-like (MDA-MB-468), although, the less sensitive subtype is HER2 (SKBR-3). The lethal dose (EC) was 4mM and the EC50 dose was 2mM respectively.
Gene Expression Microarray and Nano String techniques have been utilised in this project, which revealed on several biomarkers that were significantly up regulated in both breast cancer phenotypes. Protein Tyrosine Kinase 2 Beta (PTK2B) was the most substantial biomarker, which involved in several fundamental biological processes including proliferation and metastasis has been selected as an ideal candidate for small molecules treatment in breast cancer.  PTK2B promoting invasion and migration, while lessening the proliferation of HER2 breast cancer cells. It is also, plying a vital role in Autocrine Somatotropin signaling pathway in breast cancer.
xCELLigence System (RTCA) assay, wound-healing assay, and Cultrex® BME Cell Invasion assay were used to evaluate the role of PTK2B in breast cancer proliferation, invasion and metastasis.
Additionally, Mass Spectrometry (MS) analyses and pathways enrichment analysis have emphasise the PTK2B role in breast cancer invasion and metastasis.
The combined action of both PTK2B and metformin treatment on fundamental biological functions was also assessed in breast cancer. Metformin might be suitable treatment in some breast cancer phenotypes, however it can be antagonistic biologically and clinically in other types of breast cancer such as HER2 through enhancing crucial molecules, which driving essential biological functions including cancer initiation and dissemination

This seminar is hosted by Professor Graham Ball

All welcome.

For any enquiries please contact Dr John Dickenson

Location details

Room/Building:

282, Erasmus Darwin

Address:

Nottingham Trent University
Clifton Campus
Clifton Lane
Nottingham
NG11 8NS

Past event

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