Triple negative breast cancer (TNBC), which does not express the
progesterone,
estrogen, or HER2/
neu receptor, is aggressive and difficult to treat.
Paclitaxel, a
tubulin stabilizing agent, is one of the most frequently prescribed
anticancer agents for breast
cancers, including TNBC. Residual disease that occurs due to resistance or partial resistance of
cancer cells in a
tumor against
anticancer agents is the most important issue in oncology. In the present study, when MDA-MB-231 cells, a TNBC cell line, were treated with 30 µM
paclitaxel, a slightly higher concentration than its GI50 value, for 6 days, a small number of cells with different morphologies survived. Among the surviving cells, small round cells were isolated, cloned, and named MDA-MB-231-JYJ cells. MDA-MB-231-JYJ cells were observed to be highly proliferative and tumorigenic. In addition, signal transduction molecules involved in proliferation, survival,
malignancy, or stemness of
cancer cells, such as c-Src, c-Met, Notch 1, c-Myc, Sox2, Oct3/4, Nanog, and
E-cadherin were highly expressed or activated. While further study is required, MDA-MB-231-JYJ cells appear to have some of the characteristics of
cancer precursor cells. Although MDA-MB-231-JYJ cells were isolated from the cells that survived in the continuous presence of
paclitaxel, they were not resistant to
paclitaxel but developed resistance to
dasatinib, a Bcr-Abl and
Src kinase family inhibitor. The activated state of Src and Notch 1, and the expression levels of c-Myc and
cyclins in MDA-MB-231-JYJ cells were less affected than MDA-MB-231 cells by the treatment of
dasatinib, which may explain the resistance of MDA-MB-231-JYJ cells to
dasatinib. These results suggest that
cancer cells that become resistant to
dasatinib during the process of
paclitaxel therapy in patients may appear, and caution is required in the design of clinical trials using these two agents.