The HCC1428 breast cancer cell line was derived from the pleural effusion metastasis of a 49 year old Caucasian female patient previously diagnosed with breast adenocarcinoma. This is an ER-positive HER2 negative cell line and its expression profile indicates that it is of the luminal lineage. The STR profile and links to the complete genomic profile of these cells can be found at Cellosaurs, at COSMIC, or at DepMap portal.
Oncogene Signature:
As expected for an ER-positive luminal breast cancer cell line, HCC1428 cells have a very high level overexpression of the ESR1 gene and the gene was a strong hit in both functional screens. In addition to ESR1, the cell line has 5 candidate oncogenes with low level amplifications and overexpression in which the genes were hits in the CRISPR screen but not the RNAi screen, with the possible exception of UBR5. None of the other candidate oncogenes with genomic alterations came close to being classified as essential in either screen. Reminder that AURKA is a common essential in the CRISPR screen but not the RNAi screen, so the functional significance of this gene amplification is uncertain at best. These cells appear to be wild-type for TP53, which isn’t uncommon in ER-positive breast cancer cells. Finally, the Cellosaurus data base lists this cell line as having a gene fusion involving SLC37A1-ABCG1 genes the functional significance of which is completely unclear at this time. This is a particularly interesting cell line because as you will see below, despite the high level overexpression of ESR1 and the essentiality of this gene in these cells, this cell line is quite resistant to estrogen-receptor targeted drugs and thus is an excellent cell line in which to study intrinsic resistance to a drug that targets a highly essential gene.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| ESR1 | -1.387242538 | -0.672759758 | 4.95450119 | 0.2831 | ||
| RAD21 | -1.24781822 | -0.190570307 | 1.032608534 | 1.3608 | ||
| AURKA | -1.09803305 | -0.284062312 | 1.268773336 | 1.6581 | ||
| UBR5 | -0.933792371 | -0.57826419 | 1.117656982 | 1.3382 | ||
| RAD51C | -0.606570073 | -0.201054829 | 1.188630268 | 1.1359 | ||
| AGO2 | -0.54322787 | -0.102628793 | 1.563124662 | 1.5782 | ||
| LYN | -0.176002975 | 0.029913127 | -2.606451556 | 1.3272 | ||
| GNAS | -0.163627227 | -0.121083846 | 1.493888789 | 1.5294 | ||
| SOX9 | -0.132459472 | -0.049255017 | -3.293449892 | 1.0849 | ||
| MSI2 | -0.055914302 | -0.10632617 | 1.156304631 | 1.1359 | ||
| KDM5A | -0.02152596 | 0.073831137 | 1.460906197 | 1.0789 | ||
| RNF43 | 0.006671895 | -0.129977494 | 1.886110402 | 1.1359 | ||
| SPOP | 0.03222599 | -0.088651942 | 1.000246172 | 1.1066 | ||
| SMAD4 | 0.041984027 | -0.049445486 | -0.121673349 | -1.183 | p.EKK49del | 32 |
| GNA13 | 0.058268536 | 0 | 1.504809378 | 1.0849 | ||
| NBN | 0.058525206 | 0.074999361 | 1.55936479 | 1.3382 |
HCC1428 drug sensitivities. Despite the fact that this cell line exhibits overexpression of ESR (ER-alpha) that was found to be essential in both screens, and that the cells exhibit the expression profile of luminal breast cancer, these cells are resistant to almost all targeted drugs including those that target the ER-alpha. The GDSC2 data set indicates resistance of these cells to essentially all targeted drugs including those that target the ER. In the GDSC1 data set, there is a suggestion of moderate sensitivity of the cells to fulvestrant, but no other targeted drugs. Thus, these results suggest that this breast cancer cell line is intrinsically drug resistant despite overexpressing the ER, which again, is an essential gene in these cells.
