Background
Methods
EC cell lines and cell culture
Cell line somatic mutation genotyping
Cell viability assays
Protein extraction and reverse phase protein Array (RPPA)
Statistical analysis
Results
Genomic and proteomic features of the endometrial cancer cell lines
Cell Line | Mutational status | PTEN expression | PI3Ki Pictilisib (uM) | PI3K/mTORi Apitolisib (uM) | MEKi Cobimetinib (uM) | Combination of Pictilisib:Cobimetinib (uM) | Combination of Apitolisib:Cobimetinib (uM) | ||
---|---|---|---|---|---|---|---|---|---|
IC50 | IC50 | IC50 | IC50 | CI at ED75 | IC50 | CI at ED75 | |||
SKUT2 | PIK3CA only | High | 0.413 | 0.196 | 0.101 | 0.096 | 0.138 | 0.049 | 0.152 |
MFE280 | PIK3CA only | High | 0.440 | 0.247 | 0.461 | 0.207 | 0.357 | 0.091 | 0.528 |
EN1078D |
PTEN + PIK3R1
| High | 0.242 | 0.079 | 0.178 | 0.103 | 0.634 | 0.057 | 0.468 |
MFE296 |
PTEN + PIK3CA
| High | 0.273 | 0.106 | 0.301 | 0.383 | 1.037 | 0.120 | 0.650 |
ETN1 |
PTEN
| High | 0.544 | 0.387 | 1.077 | 0.174 | 0.426 | 0.177 | 0.495 |
AN3CA |
PTEN + PIK3R1
| Low | 0.057 | 0.028 | 0.518 | 0.339 | 0.129 | 0.070 | 0.142 |
HEC59 |
PTEN + PIK3R1
| Low | 0.189 | 0.018 | 3.289 | – | – | – | – |
EN |
PTEN + PIK3CA + PIK3R1
| Low | 1.597 | 0.548 |
36.511
| 3.117 |
1.555
| 2.175 |
1.200
|
HEC1A |
KRAS + PIK3CA
| High | 2.054 | 0.214 | 0.012 | – | – | – | – |
HEC1B |
KRAS + PIK3CA
| High | 0.798 | 0.704 | 0.033 | 0.050 | 0.031 | 0.054 | 0.035 |
HEC50 |
KRAS + PIK3R1
| High | 0.247 | 0.210 |
0.001
| 0.131 |
4.921
| 0.169 |
6.613
|
EFE184 | WT for all | High | 0.372 | 0.368 | 0.149 | 0.074 | 0.433 | 0.157 | 0.328 |
KLE | WT for all | High | 2.796 | 7.253 | 39.337 | 0.644 | 0.142 | 0.144 | 0.005 |
Groups | Cell line |
PIK3CA
|
KRAS
|
PTEN
|
PIK3R1
|
PIK3R2
| PTEN expression |
---|---|---|---|---|---|---|---|
Group 1 (PIK3CA-mutated only) | SKUT2 | E545K (hetero) | Wild-type | Wild-type | Wild-type | Wild-type | High |
MFE280 | H1047Y (hetero) | Wild-type | Wild-type | Wild-type | Wild-type | High | |
Group 2a (PTEN-mutated, PTEN-retained) |
EN1078D
| Wild-type | Wild-type | Y88C | G376R (hetero) | Wild-type | High |
MFE296 | P539R (hetero); I20M (hetero) | Wild-type | R130Q (homo); N322 fs (hetero) | Wild-type | Wild-type | High | |
ETN1
| Wild-type | Wild-type | I122V (hetero), R130L (hetero); N328 fs (hetero) | Wild-type | Wild-type | High | |
Group 2b (PTEN-mutated and PTEN-Loss) | AN3CA | Wild-type | Wild-type | R130fs (homo) | REID557del (hetero) | Wild-type | Low |
HEC59 | Wild-type | Wild-type | Y46H (hetero); R233 (hetero); P246L (hetero) | T473S (hetero); K567E (hetero); S460 fs (hetero) | Wild-type | Low | |
EN | T1025A (hetero) | Wild-type | K266 fs (hetero) | N260S (hetero) | Wild-type | Low | |
Group 3 (KRAS-mutated) | HEC1A | G1049R (hetero) | G12D (homo) | Wild-type | Wild-type | Wild-type | High |
HEC1B
| G1049R (hetero) | G12D (homo) | Wild-type | Wild-type | Wild-type | High | |
HEC50
| Wild-type | G12D (hetero) | Wild-type | E468InsGEYDRLYE (homo) | Wild-type | High | |
Group 4 (Wild-type) | EFE184 | Wild-type | Wild-type | Wild-type | Wild-type | Wild-type | High |
KLE
| Wild-type | Wild-type | Wild-type | Wild-type | Wild-type | High |
Sensitivity of endometrial cancer cell lines to two PI3K inhibitors and a MEK inhibitor
Sensitivity of EC cell lines to the two PI3K inhibitors and a MEK inhibitor in combination
Classification of endometrial cancer cell lines
-
Group 1 (PIK3CA mutated EC cell lines): SKUT2, MFE280.
-
Group 2 (PTEN mutated EC cell lines):a.(PTEN mutated EC cells with retained PTEN): EN-1078D, MFE296, ETN1.b.(PTEN mutated EC cells with PTEN Loss): AN3CA, HEC59, EN.
-
Group 3 (KRAS mutated EC cells): HEC1A, HEC1B, HEC50.