The MDA-MB-231 breast cancer cell line is perhaps the second most popular breast cancer cell line, as it was often used as the ER-negative counterpoint to the MCF-7 cells in many papers. While for many years, this seemed reasonable, we now know that MDA-231 cells represent a relatively rare sub-type of ER-negative breast cancer, the claudin low subtype, and thus is a the opposite end of the differentiation spectrum from MCF7 cells. The MDA-MB-231 cell line was derived from the pleural effusion metastasis of a 51 year old Caucasian female. The cell line is ER-negative and HER2 negative and has been variably classified as either a basal B or a claudin low subtype. In either case, the line is representative of the most aggressive type of triple negative breast cancer cell line. The STR profile along with other data and information pertinent to this cell line can be found here at Cellosaurus, or here at COSMIC, or here at DepMap portal.
Oncogene signature: The Oncogene Signature shown below is one that might be expected for a highly aggressive, basal type, metastatic breast cancer cell line. These cells have a common KRAS mutation which was a strong screen hit, a less common BRAF mutation which was also a hit in the CRISPR screen, and mutations in two tumor suppressor genes; TP53 and NF1. It is thus, not surprising that these cells are highly resistant to EGFR inhibitors or other small molecule inhibitors of the MAPK pathway.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| KRAS | -1.260588131 | -0.488576174 | -0.662291891 | -0.155 | p.G13D | 3291 |
| BRAF | -0.550268386 | 0.16068827 | 0.036308827 | 0.2717 | p.G464V | 14 |
| CCND3 | -0.325881554 | -0.245473628 | 1.567222941 | 1.0993 | ||
| NF1 | -0.272693903 | 0.016182046 | -1.132285985 | 0.0712 | p.T467fs | 8 |
| TP53 | -0.049551699 | -0.373761992 | 0.241107128 | 0.0917 | p.R280K | 154 |
| PIM1 | 0.128922776 | 0.102740801 | 1.479088333 | 1.1068 | ||
| CDKN1A | 0.177851853 | 0.042030413 | 1.69605588 | 1.1068 |
MDA-231 drug sensitivity. For many years, the breast cancer literature was filled with thousands of papers in which the MDA-231 cell line was used as the ER-negative counterpoint to the MCF-7 cell line, and therefore, it is not surprising that this cell line is not particularly sensitive to targeted drugs. In Tier 1, the BIRC3 oncogene is highly overexpressed and the cells are sensitive to a BIRC3 inhibitor, but this was only observed in the GDSC1 data set. There are not Tier 2 targeted drugs, and Tier 3 drugs includes the LCL161 drug because it targets both BIRC3 and XIAP. XIAP is an intriguing target in triple negative breast cancer cells. Finally, once again in this basal/claudin low breast cancer cell line, the GDSC1 data set indicates high sensitivity of this cell line to two different PORCN targeted drugs.
| MDA-231.T1 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | ||
| LCL161 | BIRC3 | -3.832136 | -0.285168 | 0.4677 | 3.117564205 | NULL | 0 | ||
| MDA-231.T2 | |||||||||
| None | |||||||||
| MDA-231.T3 | |||||||||
| Drug name | Gene SymbolHGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| LCL161 | BIRC3 | -3.832136 | -0.285168 | 0.4677 | 3.117564205 | NULL | 0 | 0.231802328 | -0.000548801 |
| LCL161 | XIAP | -3.832136 | -0.285168 | -0.2376 | -0.223030832 | p.Q492fs | 0 | 0 | -0.098504174 |
| Wnt-C59 | PORCN | -2.192105 | 0.226542 | 0.2675 | 2.197392976 | NULL | 0 | 0 | 0.242990822 |
| LGK974 | PORCN | -2.326036 | 0.313996 | 0.2675 | 2.197392976 | NULL | 0 | 0 | 0.242990822 |
