Smad3 shows anti-tumor activity in breast cancer cells
2014
Northwestern University Feinberg School of Medicine, Chicago, USA
Cyclin D1/CDK4 activity is upregulated in 50% of breast cancers and is involved in the inhibition of Smad3. However, it is still unclear whether how CDK4 inhibition can modulate Smad3-dependent cell/colony growth and apoptosis in breast cancer cells. Here, human breast cancer cells overexpressing cyclin D1 were used to investigate if CDK4 inhibitor, doxorubicin, modified Smad3 or a combination therapy could impact cancerous activity in these cells. The results showed that the combination therapy or the overexpression of Smad3 resistance to CDK4 phosphorylation lead to a decrease in colony formation and an inhibition of various cancer cell-related features. Moreover, the overexpression of the mutated Smad3 combined with doxorubicin treatment caused the greatest increase in the expression of apoptotic-related proteins. Overall, the researchers suggest an important Smad3 tumor suppression activity that can be synergistically complemented with doxorubicin treatment in cyclin D1-overexpressing cancer cells and point to CDK4 as a potential novel target in cancer therapy.
CDK4 inhibition and doxorubicin mediate breast cancer cell apoptosis through Smad3 and survivin
Jacqueline S Jeruss
Added on: 11-01-2021
[1] https://www.tandfonline.com/doi/full/10.4161/cbt.29693[2] https://data.jrc.ec.europa.eu/dataset/ffebe454-ed9a-47cf-8a33-8cf70c1b7d38
