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Node status Tumour size Histologic grade Estrogen receptor Progesterone receptor IGF-IR Marrow micromets. ErbB-2 expression EGF-R TP53 mutations Cathepsin D Telomerase activity PAI-1 level. Prognostic Factors in Breast Cancer; Many Identified; Examples:. Nature 406:747-752,2000
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Node status Tumour size Histologic grade Estrogen receptor Progesterone receptor IGF-IR Marrow micromets ErbB-2 expression EGF-R TP53 mutations Cathepsin D Telomerase activity PAI-1 level Prognostic Factors in Breast Cancer; Many Identified; Examples:
Nature 406:747-752,2000 • PNAS 98:10869-10874, 2001 ERBB2 GRB7 TNF-receptor-associated factor 4 TGFB1-induced anti-apoptotic factor 1 transferrin receptor p90 V-myb homolog integral membrane transporter hydrolase conjugase nucleolar protein p40 Cadherin 3 Laminin keratin 17 keratin 5 troponin I TGF beta 2 GRO1 oncogene, alpha CD36 antigen collagen glutathione peroxidase 3 plasma lipoprotein lipase integrin, alpha 7 retinol-binding protein 4 Putative G-coupled receptor Estrogen receptor trefoil factor 3 GATA-binding protein 3 X-box binding protein 1 LIV-1 NAT1 arylamine
”Survival or RFS ”endpoints” ”Metastatic potential” Lymph node status ”Therapy effect” TP53 Mutations ”Growth rate”
Cell cycle • Cyclins ( cyc D) and a cdk (like cdk4/cdk6) complex • Acting in different phases of the cycle • Influenced by inhibitors (p16, p21, p27, p57) • Amplifications – mutations • Influenced by upstream GF / Oncogenes • Some genes involved in cell cycle control (sometimes at G1 as well as G2) also involved in apoptosis (p53) • Therapy effects; growth arrest / apoptosis poorly understood
X1 X4 X2 Y1 X3 G3 Y2 G1 Z1 G2 G31 D3 Z3 D1 D31 Y21 Z2 G11 G21 D2 Y11 D23 Z31 D12 Z11 Z21 D22 D21 G111
Y1 Y3 Y2 X1 X4 X2 Y1 X3 G3 Y2 G1 Z1 G2 G31 D3 Z3 D1 D31 Y21 Z2 G11 G21 D2 Y11 D23 Z31 D12 Z11 Z21 D22 D21 G111