GENE AMPLEICATION Oncogene Amplification Source of tumor C-myc c20-fold leukemia and lung carcinoma N-myc 5-1,000-old neuroblastoma retinoblastoma -mVc 10-20-fod small-cell lung cancer C-abl -5-fold chronic myeloid leukemia C-myb 5-10-fod acute myeloid leukemia colon carcinoma c-erbB c30-fold epidermoid carcinoma K-ras 4-20-od colon carcinoma 30-60-fold adrenocortical carcinoma
GENE AMPLIFICATION Oncogene Amplification Source of tumor c-myc ~20-fold leukemia and lung carcinoma N-myc 5-1,000-fold neuroblastoma retinoblastoma L-myc 10-20-fold small-cell lung cancer c-abl ~5-fold chronic myeloid leukemia c-myb 5-10-fold acute myeloid leukemia colon carcinoma c-erbB ~30-fold epidermoid carcinoma K-ras 4-20-fold colon carcinoma 30-60-fold adrenocortical carcinoma
Ras r Locates on chromosome 11, codes for a protein with GTPase activity r relays signals by acting as a switch: When receptors on the cell surface are stimulated ras is switched on and transduces signals that tell the cell to grow. If the cell-surface receptor is not stimulated Ras is not activated and so the pathway that results in cell growth is not initiated r mutated in about 30% of human cancers so that it is permanently switched on, telling the cell to grow regardless of whether receptors on the cell surface are activated or not
Ras Locates on chromosome 11, codes for a protein with GTPase activity relays signals by acting as a switch: When receptors on the cell surface are stimulated, Ras is switched on and transduces signals that tell the cell to grow. If the cell-surface receptor is not stimulated, Ras is not activated and so the pathway that results in cell growth is not initiated. mutated in about 30% of human cancers so that it is permanently switched on, telling the cell to grow regardless of whether receptors on the cell surface are activated or not
EGR ar PDGF: EXTRACELLULAR Ras relays signals from the S EGF recepto cell surface receptors to the Grb2 SOS nucleus Tyr phosphorylation Ser/Thr phosphorvlation Ras relays signals by acting as Ras-ihdeiberident: Evens laknaseg e Raf a switch CYTOSOL I Ser phosphorylation MEK MAP: kinase kinase G AP hr/Tyr phosphor lation GTP (GTPase act ivating prot ein) ca uses GTP to be hydro lyzed 芒置 ( e nucleotide exchan ge facor) displaces GDP nact Ser/hr kinases e:g: i Rsk GTP GDP w NUCLEUS GDI nIne nui Transcation tacto ocat on inhibtor bits release of GDP Elks::Kvs
Ras relays signals from the cell surface receptors to the nucleus Ras relays signals by acting as a switch
Her2/neu/erbB-2 r This gene was discovered by three different groups. That is why it has three different names r It is a member of EgFR superfamily also be a receptor tyrosine kinases r Dr Slamon(UCla described the role of Here/neu in breast cancer and ovarian cancer r Overexpression amplification rare translocations r No ligand is known
Her2/neu/erbB-2 This gene was discovered by three different groups. That is why it has three different names. It is a member of EGFR superfamily, also be a receptor tyrosine kinases Dr. Slamon (UCLA) described the role of Her2/neu in breast cancer and ovarian cancer. Overexpression, amplification, rare translocations No ligand is known
Prospect r a breakthrough for our understanding of the molecular and genetic basis of cancer r Provided important knowledge concerning the regulation of normal cell proliferation, differentiation, and programed cell death r the identification of oncogene abnormalities has provided tools for the molecular diagnosis and monitoring of cancer r Oncogenes represent potential targets for new types of cancer therapies
Prospect A breakthrough for our understanding of the molecular and genetic basis of cancer Provided important knowledge concerning the regulation of normal cell proliferation, differentiation, and programed cell death. The identification of oncogene abnormalities has provided tools for the molecular diagnosis and monitoring of cancer. Oncogenes represent potential targets for new types of cancer therapies