tumor genes Flashcards
what are the types of cancer?
carcinoma, sarcoma, myelomas, leukemia, lymphomas, mixed types
how is cancer developed?
multistep process:
cells gradually become malignant through progressive alterations –> multiple abnormalities accumulate –> selection for grwoth advantage
what are the stages of tumor development?
tumor initiation–> tumor progression (growth advantage, survival, invasion, metastasis)
what are the causes of cancer?
carcinogens, tumor promoters
what are the characteristic properties (name 8) of cancer cells?
1.lack density dependent inhibition of proliferation
2. reduced requirements of growth factors
3.less regulated cell-cell, cell-matrix (loss of E-cadherin)
4.not sensitive to contact inhibition
5. secrete proteases and growth factors –> invasion, angiogenesis
6.dont differentiate normaly
7.do not undergo apoptosis
8.unlimited DNA replication, overexpression of telemorease
what are proto-oncogenes?
normal cell genes from which oncogenes originated
often proteins of a signal transduction pathway that controls cell proliferation –> growth factor receptors (protein-tyrosine kinases)
which signaling pathways/oncogenes play a role in cancer if they are mutated?
1.NOTCH- NICD
2. IL receptor- JAK/STAT
3. growth factor: ErbB2/HER2 receptor – RAS – either activates PI3K/Akt/mTor (inhibited by PTEN) or Raf/Mek/ERK/MAPk
4. WNT- frizzled- beta catenin-APC
what types of mutation occur in cancer?
point mutation (RAS)
abnormal chromosomes: translocation, duplications, deletions (c-myc, c-abl)
LOF in transcription factors
GOF in kinases, receptor mutations, ligand mutations
what are the properties of oncogenes?
can encode transcription factors normally induced by growth factors
proto-oncogene proteins have normal roles in growth factor stimulated signal transduction pathways
what are tumor suppressor genes?
normally they inhibit cell proliferation and tumor development
in many tumors, both genes are lost or inactivated –> contribution to an abnormal proliferation of tumor cells
how is retinoblastoma inherited?
inherited as dominat autosomal, either hereditary or sporadic
what causes retinoblastoma?
Rb1 gene encodes pRB protein
loss of pRB can lead to cancer
what is the function of pRB?
suppresses cell division in absence of mitotic signals
prevents transition from G1 to S phase
hypophosphorylated pRB: binding and inhibition of E2F –> cell cycle arrest
pRb hyperphosphorylation by CDK: release of E2F
in cancer cells disrupted pRB function results in aberrant cell proliferation
what are the types of retinoblastoma and what are their characteristics/mutations?
bilateral: both eyes –> germline mutation or sporadic
unilateral: one eye –> somatic mutation
what is the two hit model in regards to retinoblastoma?
first hit: inheritance of one defective Rb gene
second hit: only one successive genetic alteration in one of the retinal cells
tumor formation requires two genetic alterations