PROSTATE CANCER PATHWAY

Aviva Product

Not a Aviva Product

Indirect effect

Another molecule, mostly chemical compound

InhibitionDissociationPhosphorylation+pDephosphorylation-p

Nucleus

Outside

Normal prostate epithelium

Testosterone

PIP3

-p

+p+p+p+p+p+p+p

+p

+p +p

+p

+p+p

+p+p

?

Tumor growth

Other target events

DNA DNA DNA

Impaired G1 and G2 arrestReduced apoptosisGenomic instability

Genomicdamage

Hypermethylation

Cell cycleprogression

Apoptosis inhibition

Cell proliferation

Survival

Dihydrote-stosterone

Otherligands

Proliferative inflammatory atrophy

Prostatic intraepithelial neoplasia

Localized prostate cancer

Metastatic prostate cancer

(Therapeutic decreasedtestosterone and

dilydrotestosterone)

Androgen-independentcancer

Pathway diagram below is compiled from data from the Kyote Encylopedia of Genes and GenomesKanehisa, M., Goto, S., Furumichi, M., Tanabe, M., and Hirakawa, M.; KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 38, D355-D360 (2010). Kanehisa, M., Goto, S., Hattori, M., Aoki-Kinoshita, K.F., Itoh, M., Kawashima, S., Katayama, T., Araki, M., and Hirakawa, M.; From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res. 34, D354-357 (2006). Kanehisa, M. and Goto, S.; KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 28, 27-30 (2000). 2011 Aviva Systems Biology

Androgen and estrogen metabolism

SRD5A2

Carcinogens

Prostatic epithelial cell

Genetic alterationsOncogenes: ARTumor supressors:CDKN1B, NKX3.1, PTEN

Cell proliferation

Cell survival DNA

G1/S progression

DNA DNA DNA

Apoptosis

Cell Cycle

Cell Cycle

p53 signalingpathway

MAPK signalingpathway

Cytokine-cytokinereceptor interaction

CBP

TCF/LEF P53

CDK2

p27

E2F Rb

GSTP1

MDM2GSK3IKK

GF

Ras

Raf

MEKERK

AR

ARAR

SOS Grb2 PI3K

PTEN

PDK1

Casp9BADFKHR

IkBNFkB

CREB-Catenin

mTOR

NKX3.1

GFR

PKB/Akt

PSA BCL2 CyclinD1

p21p27

CyclinE

HSP