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The making and unmaking of stem-like, aggressive breast cancer cells

Date:
August 9, 2012
Source:
University of Colorado Denver
Summary:
Progestins regulate miRNA-29, returning hormone-dependent breast cancer cells to chemoresistant, aggressive, stem-cell-like state.

Reverting to a stem-like state, as shown here, helps breast cancer cells evolve around the blockages of current treatments.
Credit: Flickr/CodonAUG cc license

Breast cancers that depend on the hormones estrogen and progesterone are susceptible to treatments targeting these hormones. Take away this dependence and you lose a valuable treatment option.

A University of Colorado Cancer Center study published as a featured article in the journal Oncogene shows how progesterone does just this -- by suppressing a key microRNA, progestins return breast cancer cells to a stem-cell-like state in which they haven't yet differentiated, and are thus more resistant to chemotherapies and more likely to carry a poor prognosis.

"The reason we were looking into the possible role of microRNAs in the dedifferentiation of breast cancer cells into this aggressive, chemo-resistant phenotype is that microRNAs tend to be good, druggable targets. Because one microRNA may regulate many genes involved in a cancerous signaling pathway, we hoped to find one target with many beneficial effects," says Diana Cittelly, PhD, postdoctoral fellow at the CU Cancer Center and the paper's first author. The study was a collaboration between the CU Cancer Center labs of Jennifer Richer, PhD, and Carol Sartorius, PhD.

Specifically, the study shows that progestins regulate miRNA-29 -- a molecule that helps to decide which of a cell's genes are and are not turned into proteins. This regulation of miRNA-29 creates a cascade that stimulates breast cancer cells to revert back to a stem-like state, marked by proteins CD44 and CK5. In animal models, these stem-like cells helped breast cancer evolve around the blockages of current treatments..

"We can manipulate this miRNA-29 in cell lines," Cittelly says, "and we hope technology isn't too far in the future that will allow us to deliver miRNA-29 in human cancers as well."

Turn off the role of miRNA-29 and the hope is that breast cancers won't be able to gain stem cell-like traits and lose their hormone dependence.


Story Source:

The above story is based on materials provided by University of Colorado Denver. The original article was written by Garth Sundem. Note: Materials may be edited for content and length.


Cite This Page:

University of Colorado Denver. "The making and unmaking of stem-like, aggressive breast cancer cells." ScienceDaily. ScienceDaily, 9 August 2012. <www.sciencedaily.com/releases/2012/08/120809133851.htm>.
University of Colorado Denver. (2012, August 9). The making and unmaking of stem-like, aggressive breast cancer cells. ScienceDaily. Retrieved April 23, 2014 from www.sciencedaily.com/releases/2012/08/120809133851.htm
University of Colorado Denver. "The making and unmaking of stem-like, aggressive breast cancer cells." ScienceDaily. www.sciencedaily.com/releases/2012/08/120809133851.htm (accessed April 23, 2014).

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