SUM149PT Cells

The SUM149PT cell line is derived from a human inflammatory breast carcinoma (IBC), which represents an aggressive subtype of breast cancer. IBC is characterized by rapid progression, early metastasis, and poor prognosis. SUM149PT cells are classified as triple-negative breast cancer (TNBC), lacking expression of estrogen receptor (ER), progesterone receptor (PR), and HER2 receptor, making them unresponsive to common targeted therapies like endocrine treatments or HER2 inhibitors. Instead, treatment for such cancers typically involves cytotoxic chemotherapy, although these cancers frequently develop resistance over time.

Significantly, SUM149PT cells possess a 2288delT BRCA1 mutation, leading to a loss of BRCA1 function. This mutation is a frame-shift deletion that results in premature termination of the BRCA1 protein, impairing DNA repair and promoting genomic instability, a hallmark of BRCA1-mutated cancers. The loss of BRCA1 contributes to the heightened chromosomal instability observed in SUM149PT, which displays numerous chromosomal aberrations. In addition to the mutation, the BRCA1 locus is lost in SUM149PT, further compounding the impact on genomic stability.

Surprisingly, SUM149PT cells exhibit a CD44+/CD24-/Low stem-like cancer cell subpopulation, which is enriched in cancer stem cell (CSC) properties such as increased invasion, tumorigenesis, and resistance to chemotherapy. These stem-like cells are also associated with centrosome amplification and elevated cyclin E/Cdk2 activity. Inhibition of Cdk2 in SUM149PT selectively targets this CSC subpopulation, restoring some sensitivity to chemotherapy, which suggests that combined therapeutic strategies targeting Cdk2 and conventional chemotherapy might be effective in treating chemoresistant IBC.