Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Setting the gene expression base-line for breast cancer research

03.05.2004


For several years, scientists have attempted to identify gene expression changes, using microarrays or ’DNA chips’, in order to understand and predict breast cancer onset, progression, and clinical outcome. Although important insights into breast cancer have been drawn from determining the expression ’profiles’ of thousands of genes in tumors, the interpretation of experimental results has been complicated by the absence of knowledge about the gene expression in ’normal’, non-cancerous, breast cells. However in a paper published today in the journal Cancer Research, a team of scientists from The Breakthrough Toby Robins Breast Cancer Research Centre at The Institute of Cancer Research (ICR) in London, and the Breast Cancer Laboratory of Ludwig Institute for Cancer Research (LICR) and University College London report that they have now elucidated the expression profiles of over 6000 genes in the two primary types of normal breast cells.



The majority of breast cancers originate in an internal structure of the breast, the terminal duct-lobular unit, which is comprised of two different types of cell; the inner ’luminal’ cells, potential milk-secreting cells, in which cancerous genetic changes occur; and the surrounding basal layer of contractile ’myoepithelial’ cells. The LICR/Breakthrough team separated and purified the two cell types from material from breast reduction surgery, and showed that the cell types have distinct and quite different gene expression profiles.

"The problem is that the vast majority of breast cancer experiments have used tumor samples because that was usually the only material available," explains LICR’s Dr. A. Munro Neville, one of the senior authors of the study. "But tumors actually have different mixtures of normal luminal cells, normal myoepithelial cells, and cancer cells. Now we not only know that these cells have very different gene expression changes, we actually know the base-line expression of genes in both the normal cell types. So we can go back through all the data from the experiments with tumor samples, and discriminate between the genetic changes due to cell type differences and genetic changes due to cancer." Another important finding from the study was the identification of differences between luminal cells taken from primary breast samples and luminal cells cultured in the laboratory to which, for many ethical and logistical reasons, scientists frequently have to resort when performing experiments. The LICR/Breakthrough study results sound a cautionary warning for interpreting microarray data from cultured cells, and may also be helpful in determining between real experimental observations and artefacts relating to in vitro cell culture.


The results will also help to determine smaller and more accurate classifiers of different types of tumor. Microarray analyses have previously been used to distinguish between sub-classes of breast tumors based on the differential expression of many hundreds of genes. For example, one sub-class of tumor was identified as ’basal-like’ because the tumors expressed a series of genes thought to be expressed in myoepithelial, but not luminal cells. The basal-like tumors appeared to be more aggressive, and a retrospective study showed that those patients with basal-like tumors had a poorer prognosis than those with another sub-class. Applying the base-line dataset from the normal cells to the study that originally proposed the classification, allowed the LICR/Breakthrough team to identify a handful of critical ’marker’ genes that may be better able to prospectively diagnose tumor sub-classes, and confer independent prognostic information. These markers might also indicate possible avenues of therapy.

Importantly, according to Dr. Neville, the generation of this more accurate dataset may also have a major impact on patient care. "In order to discriminate between different types of breast cancers in the pathology lab, the surgeon often has to take a sample large enough to incorporate the basal myoepithelial cell layer. If, one day, we could use a fine needle biopsy in conjunction with the novel myoepithelial markers we’ve identified, we could not only potentially improve diagnosis, but also our therapeutic approach."


This study was conducted by researchers from: The Breakthrough Toby Robins Breast Cancer Research Centre at the Institute of Cancer Research, London, UK; the Breast Cancer Laboratory of the University College London Branch of the Ludwig Institute for Cancer Research and University College London, London, UK; Istituto di Anatomia Patologica, Università di Sassari, Italy; Servizio Epidemiologia, Azienda USL 1, Sassari, Italy; Istituto di Chimica Biomolecolare, Alghero, Italy; and The Royal Marsden Hospital, London, UK.

Sarah L. White | EurekAlert!
Further information:
http://www.licr.org/

More articles from Studies and Analyses:

nachricht Real-time feedback helps save energy and water
08.02.2017 | Otto-Friedrich-Universität Bamberg

nachricht The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

A better way to measure the stiffness of cancer cells

01.03.2017 | Health and Medicine

Exploring the mysteries of supercooled water

01.03.2017 | Physics and Astronomy

Research team of the HAW Hamburg reanimated ancestral microbe from the depth of the earth

01.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>