Table 1. Ingenuity Pathways Analysis (IPA) of upstream regulators of differentially expressed genes between BC cell lines with and without knockdown of HERV-K env RNA.
| MDAMB231 | MCF-7 | SKBR3 | MDAMB435.eB1 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Upstream Regulator | p-value of overlap | Mechanistic Network | Upstream Regulator | p-value of overlap | Mechanistic Network | Upstream Regulator | p-value of overlap | Mechanistic Network | Upstream Regulator | p-value of overlap | Mechanistic Network | |
| 1 | TP53 | 1.72E-42 | 677 (22) | TP53 | 6.59E-40 | 376 (20) | TP53 | 3.95E-22 | 189 (16) | TP53 | 3.30E-11 | 234 (20) |
| MYC | 8.79E-31 | 703 (21) | MYC | 4.32E-14 | 446 (21) | MYC | 1.22E-17 | 205 (17) | MYC | 6.87E-11 | 219 (17) | |
| HNF4A | 3.96E-20 | 669 (17) | NUPR1 | 9.74E-19 | MYCN | 4.13E-14 | ||||||
| HIF1A | 1.15E-16 | 631 (20) | CCND1 | 2.76E-15 | 351 (22) | HIF1A | 2.25E-29 | 207 (18) | SREBF2 | 3.59E-10 | 183 (16) | |
| E2F4 | 3.01E-15 | JUN | 9.73E-20 | 220 (19) | ATF4 | 8.92E-10 | ||||||
| RB1 | 3.40E-15 | 343 (18) | MITF | 4.49E-09 | 142 (5) | |||||||
| SMARCA4 | 1.76E-08 | 202 (15) | ||||||||||
| CDKN2A | 1.01E-14 | 336 (18) | ||||||||||
| E2F1 | 8.47E-14 | 334 (16) | ||||||||||
| SMARCB1 | 2.20E-13 | 444 (22) | ||||||||||
| 2 | TGFB1 | 1.06E-40 | 745 (20) | TGFB1 | 4.59E-26 | 494 (22) | TGFB1 | 8.76E-37 | 277 (18) | TGFB1 | 1.96E-20 | 280 (18) |
| HGF | 7.70E-18 | 590 (16) | HGF | 2.66E-09 | 398 (24) | HGF | 3.96E-20 | 224 (17) | HGF | 1.67E-08 | 194 (16) | |
| IGF2 | 1.48E-13 | 379 (17) | TGFB3 | 1.05E-08 | 197 (15) | |||||||
| EGF | 1.08E-17 | 741 (21) | EGF | 8.77E-07 | 347 (23) | EGF | 1.67E-19 | 220 (19) | ||||
| AGT | 1.21E-17 | 184 (17) | ||||||||||
| FGF2 | 1.35E-23 | 218 (16) | ||||||||||
| 3 | beta-estradiol | 8.26E-36 | 743 (23) | beta-estradiol | 5.09E-27 | 510 (22) | beta-estradiol | 5.01E-27 | 267 (17) | beta-estradiol | 2.95E-11 | 316 (22) |
| hydrogen peroxide | 5.57E-19 | 621 (19) | hydrogen peroxide | 2.30E-08 | 434 (21) | hydrogen peroxide | 1.27E-11 | 206 (17) | ||||
| D-glucose | 9.84E-17 | 536 (18) | dihydrotestosterone | 2.00E-08 | 230 (19) | |||||||
| tretinoin | 3.86E-16 | 767 (22) | tretinoin | 1.52 E-12 | 469 (19) | tretinoin | 1.37E-23 | 279 (18) | ||||
| 4 | TNF | 1.98E-29 | 704 (19) | TNF | 5.26E-15 | 356 (17) | TNF | 5.26E-28 | 262 (18) | |||
| IFNG | 9.02E-22 | 464 (14) | IFNG | 3.38E-14 | 462 (17) | IL1B | 7.22E-21 | 246 (17) | ||||
| IL1B | 5.60E-18 | 484 (15) | OSM | 5.18E-13 | 434 (23) | OSM | 2.63E-20 | 229 (20) | ||||
| fulvestrant | 3.20E-16 | 399 (21) | salirasib | 6.08E-23 | 215 (15) | |||||||
| trichostatin A | 4.18E-16 | 452 (23) | lipopolysaccharide | 2.95E-20 | 254 (17) | sirolimus | 1.62E-10 | 248 (20) | ||||
| 5 | dexamethasone | 1.05E-28 | 711 (19) | dexamethasone | 1.42E-15 | 475 (21) | dexamethasone | 3.52E-20 | 275 (19) | 5-fluorouracil | 1.68E-08 | |
| lipopolysaccharide | 5.70E-24 | 546 (14) | cisplatin | 2.04E-13 | 467 (20) | deferoxamine | 8.81E-20 | 199 (16) | ||||
| cisplatin | 7.44E-17 | 654 (17) | valproic acid | 3.77E-13 | 449 (21) | actinomycin D | 5.39E-18 | 227 (20) | ||||
| methylprednisolone | 2.00E-21 | 519 (17) | methylselenic acid | 4.86E-17 | 471 (22) | |||||||
| 6 | ERBB2 | 1.05E-24 | 636 (20) | ERBB2 | 5.82E-16 | 344 (22) | ERBB2 | 2.66E-19 | 228 (21) | ERBB2 | 1.95E-12 | 199 (16) |
| SRC | 4.10E-18 | 197 (17) | RAF1 | 2.36E-11 | 238 (19) | |||||||
| PRKCA | 6.52E-09 | 238 (21) | ||||||||||
| 7 | KRAS | 3.14E-12 | 655 (25) | KRAS | 4.91E-19 | 428 (19) | KRAS | 8.38E-10 | 211 (19) | KRAS | 1.26E-06 | 236 (17) |
| HRAS | 1.15E-18 | 682 (25) | HRAS | 3.14E-11 | 470 (24) | HRAS | 7.48E-15 | 209 (19) | HRAS | 1.19E-10 | 193 (16) | |
| MGEA5 | 1.82E-17 | |||||||||||
| FN1 | 2.36E-16 | 590 (14) | MGEA5 | 5.75E-10 | ||||||||
| 8 | SYVN1 | 1.58E-21 | PGR | 5.55E-14 | 386 (21) | POR | 2.45E-09 | |||||
| FSH | 1.40E-18 | 691 (18) | ESR1 | 1.12E-13 | 402 (24) | SYVN1 | 2.58E-09 | |||||
| ERK | 1.98E-16 | 539 (18) | PDGF BB | 8.63E-21 | 256 (19) | PDGF BB | 7.51E-09 | 206 (20) | ||||
| estrogen receptor | 6.30E-24 | 212 (18) | EGFR | 3.71E-08 | 248 (18) | |||||||
| U0126 | 4.03E-21 | 234 (18) | U0126 | 1.10E-08 | 235 (17) | |||||||
| PD98059 | 4.85E-28 | 221(18) |
1
transcription regulator
2
growth factor
3
chemical - endogenous mammalian
4
cytokine
5
chemical drug
6
kinase
7
enzyme
8
Others including transporter, complex, group, and chemical - kinase inhibitor