Microarrays Yield Insights on Breast Cancer Genes

Scientists have used microarray technology to discover which genes might stimulate ductal carcinoma in situ (DCIS) to progress to invasive breast cancer (IBC). These results were reported at the 3rd European Breast Cancer Conference in Barcelona (Spain).

Microarray studies employ microchips bearing thousands of known single-stranded gene fragments on their surface. A microchip is incubated with RNA from tissue samples, and by observing which gene fragments attract the RNA, it is possible to tell which genes are active in the tissue samples. Analyses of the results of the microarray studies show that there are at least 100 individual genes that have significantly different levels of activity in DCIS and IBC. Many of these genes are already known to involve processes and pathways that could make them reasonable candidates as invasion-related genes.

Prof. Craig Allred, of Baylor College of Medicine (Houston, TX, USA), explained, "DCIS is very common and gives rise to most IBCs. We already know that DCIS contains many genetic defects that are responsible for its development in the first place, but we believe that there are many additional genetic defects that must occur in DCIS to cause it to progress to IBC. Identifying the important genes will be useful because finding defects in them could help doctors to predict the outcome for the patients and, more importantly, could give us targets at which we could aim treatments to prevent or suppress invasion.”

Prof. Allred noted that several integrin genes, involved in making cells stick together, appear to be switched off in invasive tumors compared to noninvasive tumors. This suggests that defects in these genes might make cells less sticky, which is probably needed in order to become invasive. Probably, there are many defects involving such processes as cell adhesion and cell motility that are required to make a normal breast cell become a malignant invasive cell. These defects may be acquired individually and accumulate over many years.

The microarray experiments have identified candidate genes that may play a role in the invasive process. Now researchers have to confirm the importance of these genes by finding the proteins encoded by them and using clinical follow-up to see whether the genetic defects seen in the tumors are related to the outcome for the patient.





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