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Cell-surface protein controls aggressiveness of cancer

Issue date: 3/13/08
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Baylin and his group wanted to study the differences between those pancreatic cancers that express and do not express E-Cadherin. He first defined two categories of pancreatic cancers - cohesive and non-cohesive.

The first has E-Cadherin expression and forms glands and ducts in the tumor. Non-cohesive do not have E-Cadherin expression and also does not form glands nor ducts.

The next step in the research was to show that when the cancers turn from cohesive to non-cohesive, there is a specific loss of E-Cadherin rather than a more general loss of all related epithelial markers.

They showed that E-Cadherin was specifically lost and not other markers of cancer in pancreatic cells.

Finally, the researchers wanted to show a possible mechanism underlying the loss of E-Cadherin.

They first looked to see if the E-Cadherin gene was mutated and found that it was not. Loss of E-Cadherin expression is not the result of it being mutated.

They looked further at epigenetic markers associated with the E-Cadherin gene. What they found is that the E-Cadherin genes of the non-cohesive pancreatic cancers had methylated promoter sequences.

Methylation is a process in much multiple carbon groups are added to the beginning of a DNA sequence of a gene to silence it, preventing its expression into protein.

The cohesive cancers had no methylation in E-Cadherin. These cells were expressing E-Cadherin and had made no effort to block the corresponding gene.

These results show for the first time a possible underlying molecular mechanism involved in making a pancreatic cancer more aggressive.

The researchers also took frozen tissue samples from patients with different pancreatic cancers and looked for E-Cadherin expression. Those that had E-Cadherin loss also had decreased survival times compared to those patients with little or no loss of E-Cadherin.

This finding shows that E-Cadherin is a clinically relevant marker that can be used to look at the progression of the cancer.

With this new knowledge, Baylin and his team hope to create new therapies targeting the progression of pancreatic cancers using E-Cadherin as their focus.
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