Cancer Biology Flashcards
(25 cards)
neoplasm definition
a new and abnormal growth resulting from autonomous cell division
benign definition
grow slowly and remain localised to the site of origin
malignant definition
invade and spread to different site
metastasis definition
multi-step process by which tumour cells move from a primary site to colonise a secondary site
tumorigenesis process
uncontrolled cell proliferation
increased growth capability
blocked differentiation
increased cell motility
acquired tissue invasion capability
loss of genomic stability
6 features that cancer cells will acquire
1- self-sufficiency in growth signals: autonomous drive to proliferate (Ras, bcr-abl, HER-2)
2- insensitivity to growth-inhibitory signals: inactivation of tumour suppressor genes that normally inhibit growth (RB)
3- evasion of apoptosis: suppress and inactivate genes and pathways that normally able cells to die (p53, bcl-2)
4- limitless replication potential: activate specific gene pathways that render them immortal even after generation of growth (telomerase)
5- sustained angiogenesis: acquire the capacity to draw out their own supply of blood and blood vessels (VEGF)
6- Tissue invasion and metastasis: acquire the capacity to migrate to other organs, invade other tissues and colonise these organs (cadherin, proteases)
oncogene definition
a gene which in certain circumstances can transform a cell into a tumour cell
mutations available of proto-oncogene
deletion/point mutation
regulatory mutation
gene amplification
chromosome rearrangement
process of tumerigenisis
uncontrolled cell proliferation
increased growth capacity
blocked differentiation
increased cell motility
acquired tissue invasion capability
loss of genomic stability
protooncogenes definition
a normal cellular gene that encodes a protein usually involved in cell growth and proliferation
tumour suppressor gene definition
a gene whose encoded protein directly or indirectly inhibits progression through the cell cycle and in which a loss-of-function mutation is oncogenic
example of a protooncogene
Ras
example of a tumour suppressor gene
RB
what is Ras
a GTPase that transduces signals from CSRs
mutation of Ras
points mutations -> hyperactive Ras that is ‘on’ all the time (dominant effect)
30% of all tumours screened carry mutation from CSRs
what is BRAF
kinase that transduces signals from CSRs
mutation of BRAF
point mutations -> hyperactive kinase activity that is ‘on’ all the time (dominant effect)
>50% all melanomas have a mutated BRAF
what is EGFR
CSR that recieves a extracellular signals
mutation of EGFR
deletion of extracellular portion
-> absence of EGF (dominant effect)
non-small cancer
Bcr gene on chr 22 + abl gene on chr 9
bcr-abl hybrid gene in Chronic Myeloid Leukaemia (CML)
philadelphia translocation
what is ERB B2
transmembrane receptor that receives signals from other cells
mutations of ERB B2
amplified in 20% of breast cancers -> poor prognosis
how does RB oncogene activation lead to cancer
2 hit hypothesis
two mutational events must occur at the same locus to result in tumorigenesis
leads to: retinoblastomas, sarcomas, bladder/ breast/ lung carcinomas
how does p53 oncogene activation lead to cancer
tetrameric transcription factor - dominant negative
germ-like mutation predispose to Li-Fraumeni Syndrome
inactivated in 50% all human cancers