A recent study published in Nature Communications revealed a possible reason behind the resistance of breast cancer cells to endocrine therapy. The study, led by Mitsuyoshi Nakao, Director of the Institute of Molecular Embryology and Genetics in Kumamoto University and Associate Professor Noriko Saitoh, and her team, showed the molecular basis of resistance in breast cancer cells is directly related to the development of distinct non-coding RNAs.
Breast cancer affects mostly women, even at young ages, and the burden of the disease is extremely high worldwide. The female hormone estrogen is responsible for the growth and proliferation of breast cancer cells that are positive for estrogen receptors (ER). Around 60 to 70% of these cells are classified as ER positive (ER+) cells and feed on the excess amounts of estrogen secreted during tumor formation. The most common endocrine therapies are those which block these receptors. However, recurrence and invasion of cancer cells occurs as a consequence of resistance to such therapies: a reality that demands special attention due to the increased incidence of resistant cells.
The researchers used ER positive, MCF7 cancer cell lines which developed resistance due to continued growth in long term estrogen deprivation (LTED). The team observed resistance was linked to the up-regulation of the ESR1 gene (coding for ER positive cells) during the adaptation period in the LTED medium, resulting in specific non-coding (NC) RNAs. Molecular analysis showed that these NC RNAs termed Eleanors (ESR1 locus enhancing and activating non-coding RNAs), created a distinct RNA focus in the nucleus of each cell, giving rise to resistant proteins.
Importantly, the team studied the positive effects of the compound resveratrol, a kind of polyphenol, which exerted a repressive effect on the Eleanors via the ER and down-regulated the ESR1 gene, that subsequently inhibited the proliferative activity of LTED cells.
These results allowed an increased insight into one of the most commonly interfaced-yet-unsolved mysteries in breast cancer treatment, with the potential to bring hope to those battling the disease.