Women diagnosed with triple negative breast cancer can benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding cyclin dependent kinase inhibitor 3, CDKN3, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). CDKN3 was also differentially expressed in bulk tumor in human breast cancer (3). CDKN3 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of CDKN3 in primary tumors of the breast was correlated with overall survival in patients with basal-like and luminal B type cancer, while within triple negative breast cancer, primary tumor expression of CDKN3 was correlated with distant metastasis-free survival in patients with mesenchymal stem-like subtype disease. CDKN3 may be of relevance to initiation, maintenance or progression of triple negative breast cancers.
Cyclin-dependent kinase inhibitor, flavopiridol, induces apoptosis and inhibits tumor growth in drug-resistant osteosarcoma and Ewing's family tumor cells