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

August 9, 2012

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 does just this – by suppressing a key microRNA, progestins return 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 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 dependence.

Explore further: Heterogeneous ER+ breast cancer models allow more accurate drug testing

Related Stories

New target, new drug in breast cancer

June 4, 2012

Many breast cancers depend on hormones including estrogen or progesterone for their survival and proliferation. Eight years of lab work at the University of Colorado Cancer Center and elsewhere suggest that the androgen (AR) ...

Recommended for you

Researchers gain insight into breast cancer drug resistance

March 24, 2017

Breast cancer's ability to develop resistance to treatment has frustrated researchers and physicians and has thwarted even the latest and greatest targeted therapies. For example, after researchers identified a disease pathway ...

In a sample of blood, researchers probe for cancer clues

March 24, 2017

One day, patients may be able to monitor their body's response to cancer therapy just by having their blood drawn. A new study, led by bioengineers at UC Berkeley, has taken an important step in that direction by measuring ...

Is there a link between telomere length and cancer?

March 23, 2017

Telomeres are regions of repetitive DNA at the end of human chromosomes, which protect the end of the chromosome from damage. Whilst shorter telomeres are hypothesized biological markers of older age and have been linked ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.