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value: 0.0566279
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constant: true
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151596
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151944
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150996
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150000
constant: true
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151392
value: 1.0
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value: 1432410.0
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value: 62464.6
name: KM_Raf_RasActive
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150252
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reactant: 150264
fast: false
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name: EGFR degradation
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150600
kinetic law: 150660
name: PI3KCA activation by IGF1R
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150288
kinetic law: 150348
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name: ERK activation by Mek
modifier: 457728
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reactant: 150312
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150408
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150948
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150228
value: 1.0
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151140
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149748
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151068
value: 1.0
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150048
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151344
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modifier: 457956
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reactant: 151332
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fast: false
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150240
value: 35954.3
name: KM_Ras_SOS
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149772
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initial concentration: NaN
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name: Ras_active
type: Species

150792
value: 1.0
name: n_PI3K_E
type: LocalParameter

150456
value: 161197.0
name: k_D_SOS_P90Rsk
type: LocalParameter

149892
is version of: P62070
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boundary condition: false
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initial concentration: NaN
initial amount: 120000.0
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name: Ras
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150192
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species: 149748
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151548
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species: 149772
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151632
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product: 151668
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name: Mek deactivation by PP2A
reactant: 151644
reversible: false

150708
type: Reaction
fast: false
modifier: 457824
reactant: 150720
kinetic law: 150768
reversible: false
reactant: 150732
product: 150744
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name: PI3KCA activation by EGF
product: 150756

150984
type: Reaction
reversible: false
modifier: 457884
modifier: 457872
reactant: 150996
product: 151032
reactant: 151008
product: 151020
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name: ERK deactivation by PP2A
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150300
stoichiometry: 1.0
species: 149796
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150528
stoichiometry: 1.0
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151608
value: 1.0
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type: LocalParameter

150732
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149736
is version of: Q07889
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initial concentration: NaN
initial amount: 120000.0
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name: D_SOS
type: Species

150480
value: 896896.0
name: KM_D_SOS_P90Rsk
type: LocalParameter

150216
value: 32.344
name: k_Ras_SOS
type: LocalParameter

151056
value: 8.8912
name: k_ERKactive_PP2A
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149820
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initial concentration: NaN
initial amount: 800.0
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name: IGFR_active
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150036
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reversible: false
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name: SOS conformational activation
reactant: 150060
product: 150084
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reactant: 150048
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151320
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species: 149904
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value: 1061.71
name: KM_RasActive_RafPP
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151356
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150780
value: 10.6737
name: k_PI3K_EGF1R
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150468
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name: n_D_SOS
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151644
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151704
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150972
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name: kd_AKT
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150816
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name: Akt activation by PI3KCA
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151668
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150336
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150084
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name: SOS activation by IGF
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150396
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value: 6086070.0
name: KM_SOS_E
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150384
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name: SOS deactivation by P90
reactant: 150396
fast: false
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modifier: 457740
product: 150420

150900
value: 1.0
name: n_AKT_PI3K
type: LocalParameter

151164
value: 0.0771067
name: k_PI3K_Ras
type: LocalParameter

149988
constant: true
value: 0.005
name: kd_PI3K_a
type: Parameter

150144
reactant: 150156
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product: 150192
kinetic law: 150204
type: Reaction
name: kRas Activation
fast: false
reversible: false
product: 150180
modifier: 457680
modifier: 457692

151464
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149712
is version of: BTO:0002058
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size: 1.0
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name: cell_nsclc
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150804
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name: KM_PI3K_EGF1R
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BIOMD0000000427
reaction: 151632
is: MODEL1209230000
name: Bianconi2012 - EGFR and IGF1R pathway in lung cancer
is part of: GO:0048009
reaction: 150708
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substance units: 225389
species: 149748
parameter: 150012
species: 149940
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notes: Bianconi2012 - EGFR and IGF1R pathway in lung cancer EGFR and IGF1R pathways play a key role in various human cancers and are crucial for tumour transformation and survival of malignant cells. High EGFR and IGF1R expression and activity has been associated with multiple aspects of cancer progression including tumourigenesis, metastasis, resistance to chemotherapeutics and other molecularly targeted drugs. Here, the biological relationship between the proteins involved in EGFR and IGF1R pathways and the downstream MAPK and PIK3 networks has been modelled to study the time behaviour of the overall system, and the functional interdependencies among the receptors, the proteins and kinases involved. This model is described in the article: Computational model of EGFR and IGF1R pathways in lung cancer: a Systems Biology approach for Translational Oncology. Bianconi F, Baldelli E, Ludovini V, Crinò L, Flacco A, Valigi P. Biotechnol Adv. 2012 Jan-Feb;30(1):142-53. Abstract: In this paper we propose a Systems Biology approach to understand the molecular biology of the Epidermal Growth Factor Receptor (EGFR, also known as ErbB1/HER1) and type 1 Insulin-like Growth Factor (IGF1R) pathways in non-small cell lung cancer (NSCLC). This approach, combined with Translational Oncology methodologies, is used to address the experimental evidence of a close relationship among EGFR and IGF1R protein expression, by immunohistochemistry (IHC) and gene amplification, by in situ hybridization (FISH) and the corresponding ability to develop a more aggressive behavior. We develop a detailed in silico model, based on ordinary differential equations, of the pathways and study the dynamic implications of receptor alterations on the time behavior of the MAPK cascade down to ERK, which in turn governs proliferation and cell migration. In addition, an extensive sensitivity analysis of the proposed model is carried out and a simplified model is proposed which allows us to infer a similar relationship …
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created:
  W3 CDTF: Tue Nov 20 18:31:02 GMT 2012
modified:
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