FABIAN 1 AND 2 Flashcards
what are sarcomas?
cancers arising in bone or in soft tissue of body (ie muscle)
how did Rous study the sarcoma virus?
filtered tumor homogenate from a cancerous chicken
transferred to a new chicken
that chicken got cancer
virus: rous sarcoma virus (RSV)
the homogenate was smaller than a cell=a virus
what makes a cell transformed? (7 things)
- immortal
- altered morphology (round)
- loss of contact inhibition (cells can grow on top of each other)
- anchorage independent growth (dont need a solid substrate to grow)
- reduced requirement for growth factors
- increased transport of glucose
- tumourgenicity (make tumours)
how can tumors be identified with imaging?
with a PET scan
radiolabelled glucose shows up where tumours are present
what is a retrovirus?
retroviruses use encoded enzymes (reverse transcriptase) to reverse transcribe their RNA genome into complementary DNA (cDNA) and then insert it into the host genome
what are the proteins coded for by viral RNA genomes?
gag gene = core proteins
pol gene = reverse transcriptase and integrase
env gene = envelope protein
what additional gene does RSV contain?
src gene
essential for triggering the formation of sarcomas
where was the src sequence found?
in both RSV infected cells and in uninfected cells
how does the pro viral DNA integrate?
randomly
how does it happen that ALV pro viral DNA causes cancer?
randomly integrated next to c-src, and then that gets transcript and packaged into new viral particle (RSV)
what are c src and v src called in this situation?
proto oncogene (c-src)
oncogene (v-src)
what type of protein is an Src protein?
a tyrosine kinase (phosphorylates specific tyrosines in substrates)
src can also autophosphorylate
what is a kinase?
an enzyme that removes high energy phosphate group from ATP and transfers it to suitable protein substate
thereby modifies the functional state of the substrate protein
what are many oncogenes?
kinases
what is selective growth advantage?
the different between birth and death in a cell population
allows cancer cells to outgrow the surrounding normal cells
what is an oncogene?
a gene that increases the selective growth advantage of a cell in which it resides
what is a proto oncogene?
a normal gene that can become an oncogene as a result of mutations or increased expression
what is a tumour suppressor?
a gene that when inactivated or lost leads to an increase in the selective growth advantage of the cell in which it resides
how is DNA of cancer cells transferred to normal cells?
by transfection
what were early experiments of transfection to identify non viral oncogenes?
chemically transformed mouse fibroblasts: NIH T3 cells, great at taking up DNA
isolate their DNA
treat the DNA with 3-methylchloranthrene (3MC), a potent carcinogen
put that into normal mouse cells
formation of a focus of transformed cells
inject into mice: the mice form tumours
how can a proto-oncogene be turned into an oncogene? (4 things)
- amplification: a genetic alteration producing a large number of copies of small segment in genome (higher levels of expression)
- insertion/deletion (indel): insertion or deletion of a few nucleotides
- translocation: a specific type of rearrangement where regions of two non homologous chromosomes are joined
- point mutations: single nucleotide substitutions
what is a driver mutation?
a mutation that directly or indirectly confers a selective growth advantage to a cell
what is a passenger mutation?
a mutation that does not confer a selective growth advantage (along for the ride)
what is special about the number of mutations?
they vary across cancers (some have a lot of mutations some very little)
