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what are oncogenes
arise from mutation or overexpression of proto oncogenes,
also can be introduced by a virus
cause cancer
what gene changes cause cancer
oncogenes
mutations in tumour suppressor genes
mutations in DNA repair genes
what are proto oncogenes
promote cell growth and cell cycle, prevent normal cell death
eg growth factors, regulatory GTPases, transcription factors
can become oncogenes when mutated
what is Ras GTPase
the gene Ras encodes this protein. Ras is a proto oncogene
Ras is commonly mutated to yield an oncogene
this oncogene is found in 20% of human cancers
explain Ras signalling
the normal protein relays a signal from growth factor receptors
mutations can result in a hyperactive ras that signals without growth factors
what are tumour suppressor geens
prevent DNA damage / persistence of mutations
slow down cell division so DNA repair can take place
what is p53
tumour suppressor gene
encodes a protein that can detect DNA damage, stop cell cycle and promote DNA repair
if too much DNA damage, p53 can trigger apoptosis
more than half of all cancers have mutations in p53
what is Rous sarcoma virus
virus isolated from chicken fibroblast sarcoma
if injected into normal chicken embryos - causes sarcomas
RSV carries an oncogene (SRC) a non receptor tyrosine kinase that promotes cell proliferation
examples of virus induced cancers
Epstein-Barr virus - LMP1 induces growth factor & suppresses cell death genes
Hepatitis B - can integrate into human genome → hepatocellular carcinoma
HPV - linked to cervical cancer, virus protein (E6) binds p53
what are BRCA1 and BRCA2
encode for proteins breast cancer type 1 & 2 that help repair damaged DNA ie. tumour suppressor genes
mutations in BRCA genes have been found in inherited forms of breast cancer
example of DNA repair gene mutations and germline cancer mutations
how is the philadelphia chromosome linked to leukemia
abnormality of chromosome 22 where part of chromosome 9 is transferred to it → makes abnormal oncoprotein
bone marrow cells containing philadelphia chromosome often found in leukemia
how can hormones contribute to cancer
hormones naturally promote cell growth in target tissues but can contribute to proliferation in some cancers
eg elevated levels of oestrogen in breast cancer, elevated levels oh hormone receptors, thyroid hormones in thyroid cancers
what is apoptosis
cell suicide eg following DNA damage or cell damage
controlled, important in development to remove unwanted/damaged cells
how does apoptosis work
enzymes (mainlyl capases) break down cell component and organelles
cell fragments removed by immune cells
how can cancer cells avoid apoptosis
many cancers overexpress proteins that can block apoptosis
eg bcl-2 (pro-survival_ found in some lymphomas and leukaemias
what are telomeres
extra DNA at ends of chromosomes that protect chromosomes
each cell division, telomeres become shorter → limits the number of cell divisions possible for normal cells
what is telomerase
adds DNA repeat units to telomeres
in stem cells and many cancer cells