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Nuclear Myosin VI - a Therapeutic Target in Breast Cancer

NCT03430024 · Status: UNKNOWN · Type: OBSERVATIONAL · Enrollment: 120

Last updated 2019-11-13

No results posted yet for this study

Summary

Gene expression, the transfer of the genetic code into cellular proteins is one of the most fundamental processes in living cells. This process is orchestrated by protein-based molecular machines, called RNA polymerases that read the DNA sequence to generate messenger RNA (mRNA), which is translated by the cellular machinery to make proteins. Our cells have evolved elaborate regulation mechanisms to control these molecular machines and a breakdown in this regulation leads to diseases such as cancer.

Recently, molecules called myosins have been discovered in the genetic storage compartment of the cell (the nucleus) where they interact with RNA polymerases to regulate protein production. This is interesting because myosins are usually found outside the nucleus transporting cellular cargo or generating muscle contraction. In breast cancer cells, myosin is abundant and interacts with the oestrogen receptor. The majority of breast cancer in the UK is oestrogen receptor positive and activation of this receptor is an important factor controlling the growth of cancer cells. Oestrogen receptor activation appears to be dependent upon myosin and this research project will investigate how myosins are targeted to specific genes and how they are themselves regulated. This will greatly enhance our understanding of the role of nuclear myosins in oestrogen receptor positive breast cancer and may identify a novel therapeutic target for future drug development.

Conditions

Interventions

OTHER

Association of Myosin VI with oestrogen receptor

1. Gene expression analysis - RNA will be extracted from 100mg of tissue and then subjected to RT-qPCR to determine the relative expression levels of several genes, including MVI and ER Targets. We will use the same approach to determine which isoforms of MVI are expressed in the tissue. 2. Protein content analysis - Total protein will be extracted from 100 mg of tissue and western-blot analysis will be used to determine the relative amounts of MVI. Moreover, we will use cell fractionation to determine relative amounts of nuclear versus cytoplasmic protein. 3. Genomic analysis - Chromatin-immunoprecipitation (ChIP) experiments we be performed upon 100 mg of tissue sample. Here we will determine the localisation of MVI on the genome within the different tissues.

Sponsors & Collaborators

  • University of Kent

    collaborator OTHER

  • Maidstone & Tunbridge Wells NHS Trust

    lead OTHER

Principal Investigators

  • Hazel Everest · Maidstone and Tunbridge Wells NHS Trust

Eligibility

Min Age
18 Years
Max Age
85 Years
Sex
FEMALE
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2019-05-05
Primary Completion
2020-12-31
Completion
2020-12-31

Countries

  • United Kingdom

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03430024 on ClinicalTrials.gov