August 10, 2012

The Making And Unmaking Of Stem-Like, Aggressive Breast Cancer Cells

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.

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