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Tuesday, July 2, 2013

Adding telomeres to the breast cancer picture

The labs of David Gilley (Indiana University School of Medicine) and of Connie Eaves (British Columbia Cancer Agency) have identified an intriguing characteristic of some breast tissue cells that may lead to novel ways to identify women at risk for developing cancer. It seems that some breast precursor cells called luminal progenitors (LPs) have unusually short telomeres.

Telomeres are bits of noncoding DNA that cap the ends of our chromosomes like tassels. Because of the way DNA is replicated, each time a chromosome is copied a bit of the end is lost. That's not a problem as long as it's just the tassel that gets docked. Eventually, though, you run out of tassel and then the cell can no longer divide properly. 

Drawing of a telomere at the end of a chromosome.

The researchers found that the shortened telomeres in the LPs were associated with greater amounts of DNA damage at the ends of chromosomes. Thus, the short telomeres might be markers for tumor-causing DNA damage.

The shortening of telomeres isn’t irreversible, there’s an enzyme called ‘telomerase’ that lengthens them. LPs also had higher levels of telomerase than other types of breast tissue, no doubt to compensate for their malfunctioning telomeres. However, the telomerase activity declined with increasing age.

The authors created the following graphic to explain their results and their speculations.

Stem Cell Reports, 1 (1), 28-37 DOI: 10.1016/j.stemcr.2013.04.003.

At the top is one type of breast cell shown in blue (a primitive basal mammary cell) with normal telomeres. Beneath it is a luminal progenitor cell (shown in red) with short telomeres. You can see that the amount of active telomerase varies with the age of the patient. Finally, at the bottom are possible paths the LP can take. It can exit the cell cycle (die), differentiate (become a mature luminal cell) or grow into a tumor. 

Obviously, this work is in the early stages. We don’t yet know how telomere length fits into the whole tumorigenesis picture. It’s just one more piece of the puzzle but one that may be worth playing with. 

Kannan, N., Huda, N., Tu, L., Droumeva, R., Aubert, G., Chavez, E., Brinkman, R., Lansdorp, P., Emerman, J., Abe, S., Eaves, C., & Gilley, D. (2013). The Luminal Progenitor Compartment of the Normal Human Mammary Gland Constitutes a Unique Site of Telomere Dysfunction Stem Cell Reports, 1 (1), 28-37 DOI: 10.1016/j.stemcr.2013.04.003.