The MCF-7 breast cancer cell line is undoubtedly the most popular breast cancer cell line in existence with well over 10,000 papers in the literature from work with this line. MCF-7 was derived from the pleural effusion metastasis of a 69 year old Caucasian female with previously diagnosed ductal carcinoma of the breast. This line was developed by Dr. Herbert Soule at the Michigan Cancer Foundation in Detroit Michigan. Incidentally, Dr. Soule also developed the MCF-10A, MCF-10F and the MCF-12A cell lines, and is likely the most impactful scientist you’ve never heard of. To learn more about Dr. Soule and the story of the MCF, read my blogs.
MCF-7 is an ER-positive, HER2 negative breast cancer cell line and has been classified as being of the luminal lineage. The STR profile along with other genomic information pertinent to this cell line, as well as a list of all of the known derivatives of MCF-7 can be found here at Cellosaurus, or here at COSMIC or here at DepMap Portal
Oncogene Signature: As can be seen in the table below, ESR1 is highly overexpressed in these cells and was a strong hit in both functional screens. Since in addition, this cell line is known to have a complex genome, there are many other candidate oncogenes that were hits in the CRISPR screen, but these genes were not hits in the RNAi screen. PIK3CA is an important oncogene mutation in these cells and was a strong hit in the CRISPR screen and barely missed the cut point in the RNAi screen.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| ESR1 | -0.781121154 | -0.781121154 | 4.193281236 | 0.072386 | ||
| RAD51C | -1.183491912 | 0 | 3.295178429 | 3.257034 | ||
| HIST2H3D | -0.953223956 | 2.773102433 | 1.14408 | |||
| PIK3CA | -0.840496119 | -0.440093034 | -0.663389399 | 0.095766 | p.E545K | 899 |
| SDHA | -0.765559659 | -0.295686889 | 1.030553229 | 1.328869 | ||
| PTPN1 | -0.634564982 | -0.241280828 | 1.396965213 | 1.787447 | ||
| BRIP1 | -0.582468434 | 0.181694919 | 3.148429957 | 4.160824 | ||
| USP8 | -0.568798471 | 0.127179899 | 1.181856935 | 1.331202 | ||
| NRAS | -0.524848874 | -0.480302041 | 1.672910988 | 1.723897 | ||
| H3F3B | -0.487750728 | -0.253868423 | 2.157680407 | 1.489133 | ||
| MSI2 | -0.450916104 | -0.372092731 | 2.134631028 | 1.543002 | ||
| CSDE1 | -0.353165776 | -0.080255335 | 1.706041639 | 1.723897 | ||
| GNAS | -0.308019919 | -0.632050964 | 1.17799252 | 1.745601 | ||
| NCOA3 | -0.300539439 | -0.091849182 | 3.526127258 | 3.847872 | ||
| PPM1D | -0.222864678 | 0.072752788 | 3.695940573 | 3.827961 | ||
| PRKAR1A | -0.157478234 | 0.123989891 | 1.303939154 | 1.551258 | ||
| RNF43 | -0.061953639 | -0.104984229 | 2.808008507 | 1.543002 | ||
| PAX5 | -0.056091348 | -0.172430702 | 0.020775394 | -0.326188 | p.D227H | 41 |
| GNA13 | 0.092320611 | 0.242852337 | 1.172234039 | 1.551258 |
MCF-7 drug sensitivity. It is interesting that the MCF-7 cell line has been used in the preclinical development of every ER-targeted drug that is now used in patients. In that regard, it is particularly interesting that MCF-7 cells are very sensitive to Tamoxifen, whereas many ER+ breast cancer cell lines are not particularly sensitive to this drug. Also, given the PIK3CA mutation, the sensitivity to Pictilisib is of interest as the cells are not particularly sensitive to Alpelisib (Z-score = -0.915). There is also a significant literature on IGF1/IGF1R signaling in these cells, and indeed they exhibit significant sensitivity to an IGF1R targeted drug. MCF-7 cells have also been reported to overexpress BCL2 and indeed, the cells are quite sensitive to a drug that targets both BCL2 and MCL1. The Tier 2 drug list as the MTOR inhibitor Rapamycin to the list of drugs to which the cells are sensitive, which is in keeping with the PIK3CA status of these cells. It should be noted however, that MTOR is a common essential gene in both screens, so for such genes, we like to see Z-scores of -2.0 or less. Finally, Tier 3 drugs include a pan-specific inhibitor of FLT3, KIT and PDGFRA. Thus, this cell line presents many opportunities for targeted drug combinations that could include one or more ER-targeted drugs.
| MCF7.T1 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | ||
| GDC0810 | ESR1 | 0 | -2.656779 | 0.072386 | 4.193281236 | NULL | 0 | ||
| Pictilisib | PIK3CA | -0.876212 | -1.544698 | 0.095766 | -0.663389399 | p.E545K | 1 | ||
| Tamoxifen | ESR1 | -2.217613 | -0.85399 | 0.072386 | 4.193281236 | NULL | 0 | ||
| BMS-754807 | IGF1R | -1.747117 | 0 | 0.794432 | 2.265719171 | NULL | 0 | ||
| CCT007093 | PPM1D | -3.796783 | 0 | 3.827961 | 3.695940573 | NULL | 0 | ||
| Obatoclax Mesylate | MCL1 | -2.007418 | 1.149644 | 1.14408 | 0.294834214 | NULL | 0 | ||
| Obatoclax Mesylate | BCL2 | -2.007418 | 1.149644 | -0.930118 | 3.600739434 | NULL | 0 | ||
| MCF7.T2 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| GDC0810 | ESR1 | 0 | -2.656779 | 0.072386 | 4.193281236 | NULL | 0 | -1.18036952 | -0.781121154 |
| Rapamycin | MTOR | 0 | -1.583755 | -0.294207 | -0.129123144 | NULL | 0 | -1.319312817 | -1.136642625 |
| Pictilisib | PIK3CA | -0.876212 | -1.544698 | 0.095766 | -0.663389399 | p.E545K | 1 | -0.840496119 | -0.440093034 |
| Tamoxifen | ESR1 | -2.217613 | -0.85399 | 0.072386 | 4.193281236 | NULL | 0 | -1.18036952 | -0.781121154 |
| MCF7.T3 | |||||||||
| Drug name | Gene SymbolHGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| Pictilisib | PIK3CA | -0.876212 | -1.544698 | 0.095766 | -0.663389399 | p.E545K | 1 | -0.840496119 | -0.440093034 |
| Pictilisib | PIK3CB | -0.876212 | -1.544698 | -0.2204 | -0.018688805 | NULL | 0 | 0.110648524 | 0.205871208 |
| SB216763 | GSK3A | -1.636864 | -0.830102 | 0.089872 | -0.010211721 | NULL | 0 | -0.402750796 | -0.023512223 |
| SB216763 | GSK3B | -1.636864 | -0.830102 | 0.108956 | -0.210897817 | NULL | 0 | -0.058096182 | 0.273356613 |
| Amuvatinib | FLT3 | -2.251525 | 0 | 0.104543 | 0.069041644 | p.C368N | 0 | -0.077174054 | 0.140508364 |
| BMS-754807 | IGF1R | -1.747117 | 0 | 0.794432 | 2.265719171 | NULL | 0 | -0.116343221 | -0.148345958 |
| BMS-754807 | INSR | -1.747117 | 0 | -0.887017 | 0.32708592 | NULL | 0 | -0.061611142 | 0.017109027 |
| Amuvatinib | KIT | -2.251525 | 0 | -0.283846 | -0.061676717 | NULL | 0 | -0.313981394 | -0.00989253 |
| Rucaparib | PARP1 | -1.551084 | 0 | 0.079421 | -0.753809454 | NULL | 0 | -0.096342057 | -0.089873491 |
| Rucaparib | PARP2 | -1.551084 | 0 | 0.438844 | 0.094685151 | NULL | 0 | 0.005168514 | NULL |
| Amuvatinib | PDGFRA | -2.251525 | 0 | -0.283846 | -0.054966459 | NULL | 0 | -0.334405403 | -0.157034483 |
| GSK650394 | SGK2 | -1.835046 | 0 | 0.41091 | -0.186011986 | NULL | 0 | 0.351431179 | -0.315878299 |
| GSK650394 | SGK3 | -1.835046 | 0 | 0.519503 | 2.006388082 | NULL | 0 | 0.226259275 | 0.082642611 |
| Obatoclax Mesylate | BCL2 | -2.007418 | 1.149644 | -0.930118 | 3.600739434 | NULL | 0 | 0.048705281 | 0.013682254 |
| Obatoclax Mesylate | BCL2L1 | -2.007418 | 1.149644 | 0.712764 | -0.547899083 | NULL | 0 | -0.31008664 | -0.038169816 |
