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Regulation of Brk/PTK6 Expression in Breast Cancer Cell Lines

Brk/PTK6 is an intracellular tyrosine kinase whose expression is up-regulated in many breast cancers and high expression has been linked to higher tumour grade. It has been shown to potentiate EGF, IGF and MET signalling pathways resulting in increased
signalling up-regulating several processes that are required for tumour development such as cellular proliferation, anchorage-independent cell growth and migration. Brk expression also results in decreased cell death. Much of the current research focuses on identifying new substrates and elucidating Brk's potential role in tumour progression and chemotherapy resistance. However, to
date there is little known about the processes that lead to Brk expression. Identification of a HIF-response element upstream of the ptk6 gene indicates that hypoxia could play a role in regulating expression, although this is unlikely to be the only mechanism. Understanding how Brk expression is regulated may lead to the identification of new targets for therapeutic intervention.

This project will focus on identifying transcription factors that are known to be involved in tumourigenesis and investigating whether they play a role in regulating Brk expression. Expression analysis will be carried out to identify transcription factor expression patterns in breast cancer cell lines which can then be correlated to Brk expression. Once individual transcription factors (or their families) have been identified, RNA interference and over expression techniques will be used to down regulate transcription factor expression and the effects on Brk expression will be determined.  In addition methylation of the Brk promoter in breast cancer cells with varied Brk expression will be examined The main techniques for this study will be cell culture, RNA interference, RT-PCR, RNA extraction, reverse transcription, western blotting and epigenetic analysis.

How to apply

If you are interested in applying for the above PhD topic please follow the steps below:

  1. Contact the supervisor by email or phone to discuss your interest and find out if you woold be suitable. Supervisor details can be found on this topic page. The supervisor will guide you in developing the topic-specific research proposal, which will form part of your application.
  2. Click on the 'Apply here' button on this page and you will be taken to the relevant PhD course page, where you can apply using an online application.
  3. Complete the online application indicating your selected supervisor and include the research proposal for the topic you have selected.

Good luck!

This is a self funded topic

Brunel offers a number of funding options to research students that help cover the cost of their tuition fees, contribute to living expenses or both. See more information here: The UK Government is also offering Doctoral Student Loans for eligible students, and there is some funding available through the Research Councils. Many of our international students benefit from funding provided by their governments or employers. Brunel alumni enjoy tuition fee discounts of 15%.