Study Elucidates Mechanisms Driving Development of Aggressive Breast Cancer

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(ChemotherapyAdvisor) – Understanding the stem cell-like behavior of certain breast tumors may lead to the development of novel therapies for the treatment of hormone-sensitive breast cancer, according to a team of researchers of The University of Colorado Cancer Center, Aurora, CO. This conclusion is based on an article entitled “Progestin suppression of miR-29 potentiates dedifferentiation of breast cancer cells via KLF4,” which was published in the July issue of Oncogene.

Stem cells are the early precursors of mature cells that have a distinct function (e.g. hepatocytes). When cancer arises, the characteristics of the tumor cells may resemble that of stem cells or be stem-like.

This design of this study is based on previous evidence demonstrating that “the female hormone progesterone (P4) promotes the expansion of stem-like cancer cells in estrogen receptor (ER)- and progesterone receptor (PR)-positive breast tumors,” the investigators wrote.

As these breast tumor cells mature, they no longer express ER and PR, but instead express the tumor-initiating marker CD44 and the progenitor marker cytokeratin 5 (CK5). The investigators aimed to determine the mechanisms underlying this hormone-stimulated reprogramming. To meet the aim of this study, the investigators studied the role of small nucleic acids known as microRNA in this process.

The investigators showed that the expansion of the CD44-positive breast tumor cells is due, at least in part, to regulation of a specific family of miRNAs. They also showed that these cells expand in response to progesterone, which explains the hormone sensitivity of breast tumors as well as their stem-like appearance.  

Decreasing the expression of specific miRNAs in breast tumors may represent a novel mechanism for treating hormone-responsive breast cancers.


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