67. Definition of tumor (oncogenesis, tumorsuppressor genes) Flashcards
Definition of tumor
pathologic lesion with IRREVERSIBLE genetic damage in the background -> abnormal cell proliferation
Neoplasia - ?
new tissue proliferation
Why we also call neoplasm tumor?
one of the main characteristics of inflammation (swelling). Tumor in Greek = “-oncos” -> oncology
Immortalisation
Progressive growth of neoplastic cells , infinite proliferation ability. But neoplasm will have resting periods when it will stay in stable state and it won’t grow for a while
Oncogenes - ?
A mutated form of a type of protooncogene, (which is involved in normal cell growth and division). Oncogenes are more active
Oncogenes are dominant (gain-of-function mutation in a single copy of the cancer-critical gene can drive a cell toward cancer)
What is special about neoplasm metabolism (Warburg effect) ?
Anaerobe glycolysis instead of aerobic
Can neoplasm apoptose?
Usually neoplastic cells lose apoptic ability (no programmed death)
What is special about neoplasm <-> blood vessels ?
Continuous angiogenesis
Inflammatory proccesses <-> neoplasm
Inflammatory processes will actually SUSTAIN neoplasm
General characteristics of carcinogenesis:
- immortalisation
- oncogenes / tumorsupressor genes
- anaerobic glycolysis > aerobic glycolysis
- loosing of apoptic ability
- continuous angiogenesis
- predisposition to tissue invasion and metastasis (malignant!)
- sustaining inflammatory processes
- genomic instability as predisposition factor
Somatic vs germinal mutation ?
Somatic - mutation in somatic cell
Germinal - mutation in a gamete during gametogenesis
spontaneous vs induced mutations
Spontaneous - error in DNA replication
Induced - environmental/epigenetic effect
Epigenetics - the study of changes in organisms caused by modification of gene EXPRESSION rather than alteration of the genetic code itself
Classification of mutations depending on amount of affected genes:
- gene mutation / pointmutation - 1 gene
- chromosome mutation - > 1 gene
- genome mutation - whole genome is affected
Do mutation always lead to carcinogenesis?
NO!
- apoptosis.
- enzyme can repair the error.
- error can occur in functionally inactive location.
- error can occur in a neutral location regarding to oncogenesis (may be alteration in function but won’t cause carcinogenesis)
What are requirements for start of carcinogenesis ?
- numerous genetic mutations (in functionally active locations)
- preservation of replication ability (transmission of genetic mutation to daughter cells, telomerase activity)
genetic instability
Mutation leads to more mutations
How do neoplastic cells maintain their proliferation ability ?
Reactivation of telomerase enzyme -> immortalization
How does telomerase function in normal cells ?
Every time cells divide, their telomeres shorten, which eventually prompts them to stop dividing and die. Telomerase prevents this decline in some kinds of cells, including stem cells, by lengthening telomeres (adding TTAGGG to 3’ end)
As cell loses its ability to proliferate (adult cell), it will lose the activity of telomerase, so chromosome will be shorter during every DNA replication, shorter chromosome - older the cell (senescence = cell aging)
Senescence - ?
aging
Main targets of carcinogenesis:
- protooncogenes =normal genes producing metabolites to help cell to proliferate
- oncogenes = mutant or highly expressed variants of protooncogenes. Have autonomous function, don’t need normal growth signals
- suppressor genes = inhibit cell proliferation through regulation of cell cycle
- stability genes = part of DNA repair mechanisms
Protooncogenes
Normal genes helping cell to proliferate
- growth factors (epidermal GF (EGF), platelets derived GF (PDGF), TGF, and more…)
- nuclear factor receptors
- signal molecules
- transcription factors
Tumorsuppressor genes
Normally inhibiting activity of proliferation of the cell
In neoplastic processes usually are inactivated (genetic mutation). These mutations are recessive (except p53) -> both alleles need to be mutated to a phenotypic manifestation
Stability genes
members of DNA repair system, maintain genomic integrity
- keep genetic variance low
- indirect tumorsuppressors
- due to stability genes mutations and inactivation, mutations rate increases in other cells
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