Terapias dirigidas en combinación con hormonoterapia en cáncer de mama avanzado HER2- negativo - page 6

 AKT and mTORC1 alter the
expression, localisation, and
stability of proteins
involved in cell cycle regulation1,2
 Stabilisation of Cyclin D and p21Cip1
results in formation of the complex
p21Cip1–Cyclin D–CDK4/6 1,2
 Inactivation of p27Kip1 relieves
inhibition of the Cyclin E–CDK2
complex1,2
 Phosphorylation of the tumor
suppressor Rb by Cyclin D–CDK4/6
and Cyclin E–CDK2 promotes cell
cycle progression3
AKT andmTORC1Activity Promote Cell Cycle Progression
CDK, cyclin dependent kinase; E2F, E2 transcription factor; mTORC, mammalian target of rapamycin complex;
Rb, retinoblastoma protein.
1. Chang F, et al. Leukemia 2003;17:590–603; 2. Liang J and Slingerland JM. Cell Cycle 2003;2:336–342;
3. Giacinti C and Giordano A. Oncogene 2006;25:5220–5227.
AKT
mTORC1
CDK4/6 Cyclin D
p21Cip1
E2F
E2F
Rb Rb
P
E2F Gene
transcripti
on
G1
G2
S
G0
M
G1/S
checkpoint
p27Kip1
CDK2 Cyclin E
1
6
0
9
0
4
3
6
8
1