Monday, May 23, 2011

HER2 Part 2: What Goes Wrong in Breast Cancer?

If you have "HER2-positive" breast cancer, then there's a huge overabundance of HER2 molecules on surface your breast tumor cells.

To paint a clearer picture, there are normally about 10,000-20,000 HER2 molecules on a breast cell. On a HER2 positive breast cancer cell, there are 1-2 million... so a 100-fold increase.

Having this many extra HER2 cells on the cell surface ready and waiting to pair up with other HER molecules upon their binding with EGF very simply sends a much louder "grow" signal inside the cell and into the nucleus. The cell grows faster and divide more often. They have one of the key characteristics of cancer cells: rapid, uncontrolled growth.

Why are there so many HER2 molecules on the cell surface? We have to look into the nucleus at the world of DNA. DNA is a long filamentous molecule. It's packaged as chromosomes (23 pairs, one from mom and one from dad, so 46 total). And it contains messages called genes that provide the code for making specific proteins. On chromosome 17 sits one of the 20,000 human genes that code human life. It is the gene that makes the HER2 protein.

In an earlier blog we talked about the fact that everything that goes awry in cancer cells, including uncontrolled growth, blood vessel formation, cell mobility, etc.... everything is due to gene mutations and problems with DNA repair.

Well, one of the general kinds of mutations that occur when a cell is having problems keeping its DNA pristine is called gene amplification. In gene amplification, one section of a very long DNA molecule starts creating extra copies of itself. The extra copies remain attached to the main strand. Visualize this as a long rope where in one section, there is a big bulge of extra rope strands. Rampant gene amplification is a common characteristic in cancer cells.

In HER2 positive cancer cells, a specific gene amplification occurs at the part of chromosome 17 where the HER2 gene sits. This results in many extra copies of the HER2 gene that in turn produce an overabundance of HER2 proteins that lodge themselves in the cell membrane, poised to send too much grow signal inside the cell.

So the answer to the question in today's title is: "Gene amplification on chromosome 17 that results in up to a 100-fold overabundance of HER2 growth factor receptor."

Next: Drugs that Target HER2

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