The MDA-MB-175VII breast cancer cell line was derived from the pleural effusion metastasis of a 56 year old African American patient previously diagnosed with infiltrating ductal carcinoma of the breast. The cell line is ER-positive and HER2 negative, and yet has been molecularly classified as belonging the HER2 subtype of breast cancer. The STR profile along with other genomic 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 for this cell line is relatively simple but has a couple of interesting features. First, as indicated above, this is an ER-positive breast cancer cell line. However, in contrast to most of the other ER-positive cell lines, the ESR1 gene was not found to be essential in these cells. In that regard, it may be relevant that the level of ER overexpression in this cell line is significantly less than for other ER positive cell lines in the panel. These cells also have a CCND1 gene amplification but once again, this gene was not found to be essential in the screen. As will be detailed elsewhere, we have so far found no relationship between amplification of CCND1 and gene essentiality using either screening method.
| Gene | CRISPR score | shRNA score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| ESR1 | -0.177961216 | 2.260178632 | -0.2938 | |||
| CCND1 | -0.334268485 | 1.480948187 | 1.6935 | |||
| BCL9 | -0.275147376 | 1.02962922 | 1.0553 | |||
| NF1 | -0.087126829 | -0.954140477 | 0.1792 | p.T676fs, p.TY2284fs | 15 | |
| PAK1 | 0.039591288 | 1.588643356 | 1.1554 |
MDA-175VII Drug Sensitivities. This is an extremely interesting and unusual breast cancer cell line from several perspectives. First, as noted above, genomically this is an ER-positive and HER2 negative breast cancer cell line, but from the perspective of the screen data and the drug sensitivity data, it actually behaves like an ER-negative/HER2 positive breast cancer, and in that regard, it’s interesting that the expression profile of these cells puts in the HER2 subtype. The ESR1 gene was not a hit in the screen, and indeed, these cells are overtly resistant to ER targeted drugs. By contrast, despite the fact that ERBB2 is not amplified in these cells, it was a hit in the screen, and the cells are highly sensitive to ERBB2 targeted drugs and to AKT targeted drugs. In this regard, it is interesting that ERBB3 is overexpressed in these cells, and if one looks into this further using the Gene Query tool, one can see that the ERBB3 ligand NRG1 is highly overexpressed. These results suggest that the HER2 subtype of these cells, the essentiality of ERBB2, and the sensitivity to ERBB2 targeted drugs is mediated in these cells by ligand driving activation of ERBB2/ERBB3 heterodimers, which in this case, mimics ERBB2 gene amplification. I don’t know of any other breast cancer cell line that behaves in this manner, and one wonders how many primary breast cancers that do not have a ERBB2 amplification but for which their expression profile puts them in the HER2 enriched subtype behave in this manner.
| MDA-175VII.T1 | |||||||||
| None | |||||||||
| MDA-175VII.T2 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| Afatinib | ERBB2 | -2.763569 | -3.68811 | 0.1792 | 1.761804294 | NULL | 0 | NULL | -0.518655663 |
| Sapitinib | ERBB2 | 0 | -2.979268 | 0.1792 | 1.761804294 | NULL | 0 | NULL | -0.518655663 |
| Sapitinib | ERBB3 | 0 | -2.979268 | 0.0504 | 1.348712701 | NULL | 0 | NULL | -0.97494606 |
| Lapatinib | ERBB2 | 0 | -2.804677 | 0.1792 | 1.761804294 | NULL | 0 | NULL | -0.518655663 |
| Afuresertib | AKT1 | 0 | -1.776819 | 0.3259 | 0.64194448 | NULL | 0 | NULL | -0.54414539 |
| MK-2206 | AKT1 | -2.416096 | -1.644914 | 0.3259 | 0.64194448 | NULL | 0 | NULL | -0.54414539 |
| Ipatasertib | AKT1 | 0 | -1.589722 | 0.3259 | 0.64194448 | NULL | 0 | NULL | -0.54414539 |
| CP724714 | ERBB2 | -4.419212 | 0 | 0.1792 | 1.761804294 | NULL | 0 | NULL | -0.518655663 |
| CI-1033 | ERBB2 | -2.789112 | 0 | 0.1792 | 1.761804294 | NULL | 0 | NULL | -0.518655663 |
| PF-00299804 | ERBB2 | -3.274614 | 0 | 0.1792 | 1.761804294 | NULL | 0 | NULL | -0.518655663 |
| MDA-175T3 | |||||||||
| Drug name | Gene SymbolHGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| Afatinib | EGFR | -2.763569 | -3.68811 | 0.4882 | -1.510104993 | NULL | 0 | NULL | 0.02049108 |
| Sapitinib | EGFR | 0 | -2.979268 | 0.4882 | -1.510104993 | NULL | 0 | NULL | 0.02049108 |
| Lapatinib | EGFR | 0 | -2.804677 | 0.4882 | -1.510104993 | NULL | 0 | NULL | 0.02049108 |
| Osimertinib | EGFR | 0 | -2.505756 | 0.4882 | -1.510104993 | NULL | 0 | NULL | 0.02049108 |
| Gefitinib | EGFR | -1.276496 | -2.477898 | 0.4882 | -1.510104993 | NULL | 0 | NULL | 0.02049108 |
| Afuresertib | AKT3 | 0 | -1.776819 | 0.9391 | -0.400671055 | NULL | 0 | NULL | 0.107241163 |
| Afuresertib | AKT2 | 0 | -1.776819 | -0.123 | -0.230365506 | NULL | 0 | NULL | -0.25629458 |
| MK-2206 | AKT2 | -2.416096 | -1.644914 | -0.123 | -0.230365506 | NULL | 0 | NULL | -0.25629458 |
| Ipatasertib | AKT3 | 0 | -1.589722 | 0.9391 | -0.400671055 | NULL | 0 | NULL | 0.107241163 |
| Ipatasertib | AKT2 | 0 | -1.589722 | -0.123 | -0.230365506 | NULL | 0 | NULL | -0.25629458 |
| Pelitinib | EGFR | -3.049884 | 0 | 0.4882 | -1.510104993 | NULL | 0 | NULL | 0.02049108 |
| CI-1033 | EGFR | -2.789112 | 0 | 0.4882 | -1.510104993 | NULL | 0 | NULL | 0.02049108 |
| PF-00299804 | EGFR | -3.274614 | 0 | 0.4882 | -1.510104993 | NULL | 0 | NULL | 0.02049108 |
| AST-1306 | EGFR | -2.896492 | 0 | 0.4882 | -1.510104993 | NULL | 0 | NULL | 0.02049108 |
| CI-1033 | ERBB4 | -2.789112 | 0 | -0.3108 | -0.087448072 | NULL | 0 | NULL | -0.014583769 |
| PF-00299804 | ERBB4 | -3.274614 | 0 | -0.3108 | -0.087448072 | NULL | 0 | NULL | -0.014583769 |
| AST-1306 | ERBB4 | -2.896492 | 0 | -0.3108 | -0.087448072 | NULL | 0 | NULL | -0.014583769 |
