miRNA-135a to detect and reverse taxane resistance in tumor cells
Children's Hospital Boston
posted on 01/07/2012
Dr. Zetter's lab screened taxane-resistant tumor cells and taxane-sensitive cells for differences in miRNA expression. They identified miR-135a as being upregulated in resistant tumor cells relative to sensitive cells. Cancer types tested included prostate cancer, breast cancer and uterine carcinoma. || Additionally, paclitaxel-resistant tumors were selected by inoculating mice with A549 lung cancer cells and treating the animals 3 times weekly with paclitaxel for 120 days. Tumors became resistant and continued to grow in the presence of paclitaxel. These in vivo-derived paclitaxel resistant tumors showed increased levels of miR-135a, confirming its importance in a model that is similar to that found in clinical practice in human patients where resistance arises over time. Additionally, the tumor cells remain exposed to the tumor microenvironment. || The researchers found that the inhibition of miR-135a with a specific inhibitor (antagomir) reversed the resistance to Paclitaxel in resistant lung cancer cells, showing that miR-135a is essential to taxane reisistance in this model.
File Number: CMCC 2258
Other Information: *Investigator(s)*
Bruce Zetter
*Contact*
Maude Tessier, Maude.Tessier@childrens.harvard.edu
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