The HCC1500 Breast Cancer Cell Line

The HCC1500 breast cancer cell line is an estrogen receptor positive, HER2 negative cell line of the luminal lineage.  It was derived from a 32 year old African American woman with ductal breast carcinoma.  The STR profile along with other data and references pertinent to this cell line can be found here at Cellosaurus or here at COSMIC, or here at DepMap Portal

The tables below were derived using the data mining tools on the SLKBase and are designed to provide rapid summaries of the oncogene signature of this cell line, and the best druggable targets for these cells.

Oncogene Signature:  The Oncogene Signature shows that these cells overexpress ESR1 which is also essential in this cell line.  The cells have a CCND1 amplification, and this gene too is essential.  Interestingly, these cells slightly overexpress KRAS, which is not mutant in these cells, but the gene still did hit in the screen indicating it’s importance to the proliferative activity of this cell line.

Gene CRISPR score Demeter score Log fold change DNA amp mutation occ. In Cosmic
ESR1 -1.043697285 5.541605976 0.376
CCND1 -0.723291063 1.837687574 2.2584
KRAS -0.55615434 1.424442316 1.1604
BCL2 -0.461873931 5.424356574 1.6478
ETNK1 -0.033214331 2.153682486 1.1604
MALT1 -0.013611167 1.898778143 1.9138
PMAIP1 0.015534729 3.380845212 1.6672
TBL1XR1 0.025801431 1.119210961 1.5087
INPPL1 0.032124927 1.747753405 1.2156
ARHGEF28 0.161668712 1.188311565 1.6187
RECQL 0.176674292 1.425066864 1.1604

HCC1500 Drug sensitivities.  The drug sensitivity profile for this cell line is interesting and unexpected given that this is a strongly ER-positive cell line in which the ESR1 gene was a strong hit in the RNAi screen, indicating that this gene is essential for these cells.  Despite that essentiality, the cells are not highly sensitive to an ER-targeted drug.  By contrast, much like other ER-positive breast cancer cells, the cells overexpress BCL1 and are highly sensitive to a number of different drugs that target BCL2.   Pay particular attention to the Z-score for Venetoclax, as this drug is specific for BCL2 and does not target other BCL2 family members.  Navitoclax, by contrast targets both BCL2 and BCL2L1, and it’s the BCL2 targeting action of this drug that accounts for it’s low Z-score.  Thus, the use of BCL2 targeted drugs in this cell line could significantly sensitize them to other ER-targeted drugs.  The other drugs to which the cells are sensitive are pan-specific drugs and the low Z-scores for these drugs were obtained from the GDSC1 screen only.

HCC1500.T1
Drug name Gene symbol_HGNC z_score_GDSC1 z_score_GDSC2 DNA_amp lfc mutation COSMIC_hit
Venetoclax BCL2 0 -3.43015 1.6478 5.424356574 NULL 0
ABT737 BCL2 0 -2.569912 1.6478 5.424356574 NULL 0
Navitoclax BCL2 -2.220053 -2.119528 1.6478 5.424356574 NULL 0
HCC1500.T2
Drug name Gene symbol_HGNC z_score_GDSC1 z_score_GDSC2 DNA_amp lfc mutation COSMIC_hit achilles_score demeter
AZD8055 MTOR -1.917062 -0.042388 -0.671 -0.67314708 NULL 0 NULL -1.426706227
HCC1500T3
Drug name Gene SymbolHGNC z_score_GDSC1 z_score_GDSC2 DNA_amp lfc mutation COSMIC_hit achilles_score demeter
ABT737 BCL2L10 0 -2.569912 -0.615 -0.07038933 NULL 0 NULL -0.091080511
ABT737 BCL2A1 0 -2.569912 -0.5748 -0.04141993 NULL 0 NULL -0.068387712
ABT737 BCL2L1 0 -2.569912 0.147 0.05361661 NULL 0 NULL -0.160962775
Navitoclax BCL2L1 -2.220053 -2.119528 0.147 0.05361661 NULL 0 NULL -0.160962775
Amuvatinib FLT3 -1.972674 0 -0.6433 0.770518154 NULL 0 NULL 0.169902954
Amuvatinib KIT -1.972674 0 0.3623 -0.06167672 NULL 0 NULL 0.049255482
Amuvatinib PDGFRA -1.972674 0 0.3623 -0.05496646 NULL 0 NULL -0.045576129
Ruxolitinib JAK1 -2.40291 0.271803 0.4204 0.287738552 NULL 0 NULL -0.050407786
Ruxolitinib JAK2 -2.40291 0.271803 -0.6589 0.511463837 NULL 0 NULL 0.08318776