Luminal Breast Cancer

Pathway ID: SIGNOR-LBCView in NDEx

Description: Breast cancer is the most frequently occurring cancer in women in the developed world, with oestrogen receptor (ER)-positive disease representing around two- thirds of all cases. In this model we focus on ER-positive/HER2- negative breast cancer who results from mutations in four main signalling pathways: 1)PI3K/AKT/mTOR pathway; 2)cyclin D1 complex/Rb/E2F pathway; 3)TP53/MDM2 pathway; and 4) FGFR1 pathway. Genes from the PI3K/AKT/mTOR pathway are the most frequently mutated in luminal breast cancer; PI3K mutations are the most prevalent mutations and are identified in around 40% of cases; In luminal tumours, inhibition of the Rb protein is mediated through CCND1 (the gene coding for cyclin D1) or CDK4 amplification or overexpression, or loss of the endogenous CDK inhibitors (CDKN2A), these muatations prevent the inactivation of the E2F transcription factor, thus leading to cell cycle progression from G1 to S phase. The TCGA showed amplification of CCND1 in 29% of patients with luminal A tumours and in 58% of patients with luminal B tumours. Moreover, two-thirds of luminal B tumours may have defective p53 pathways, either through TP53 mutations or MDM2 amplification. Finally, FGFR signalling through FGF ligand dependent or independent activation has been implicated in oncogenesis, angiogenesis and treatment resistance in various tumour types. Indeed, FGFR1 amplification has been found in up to 10% of breast cancer tumours.

Curated by: Livia Perfetto

complexity level

level 1 seed interactions
level 2 connect
level 3 first neighbors
level 4 all
level 5 PPI

32 Seed Entities

Organism:
Name Primary ID
AKT SIGNOR-PF24
BRAF P15056
CDKN2A P42771
Cell Growth SIGNOR-PH33
CyclinD/CDK4 SIGNOR-C18
CYP19A1 P11511
E2F1 Q01094
ERK1/2 SIGNOR-PF1
ESR1 P03372
estradiol CID:5757
FGFR1 P11362
FRS2 Q8WU20
G1/S transition SIGNOR-PH50
GRB2 P62993
INSR P06213
IRS1 P35568
JUN P05412
KRAS P01116
MDM2 Q00987
MEK1/2 SIGNOR-PF25
mTORC1 SIGNOR-C3
PDPK1 O15530
PIK3CA P42336
Proliferation SIGNOR-PH4
PTEN P60484
PtsIns(3,4,5)P3 CID:24755492
RB1 P06400
RHEB Q15382
SOS1 Q07889
Survival SIGNOR-PH13
TP53 P04637
TSC1/TSC2 SIGNOR-C101