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 LICRs 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.
Sarah L. White | EurekAlert!
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