8.2 - Gene expression and cancer Flashcards
What is a totipotent cell and why are they specialised?
- can divide and produce any type of body cell
- only occur for limited time in early mammalian embryos
- why specialised: only translate part of their DNA during development
e.g zygote
What is a pluripotent cell?
- can differentiate into any cell found in embryo but not extra-embryonic (placental) cells
- can divide in unlimited numbers
- used to treat human disorders
- found in embryos
What is a unipotent cell?
- adult cells that can only differentiate into a limited number of their own lineage
- found in mature mammals
e.g cardiomyocytes
(most cells in animal bodies are unipotent)
What is a multipotent cell?
- can divide to form a limited number of different cell types in unlimited numbers
- found in mature mammals
e.g bone marrow cell/adult stem cell
How can induced pluripotent stem cells (iPS cells) be produced?
- from adult somatic cells (unipotent)
- using appropriate protein transcription factors
- differentiate into all possible specialised cell types
Describe how oestrogen initiates transcription
- binds to receptors in cell membrane
- switches on genes for cell growth
- transcription factors enters nucleus from cytoplasm via nuclear pore + combines with DNA
- stimulates transcription
(increased oestrogen can cause cancer)
Define epigenetics
heritable changes in gene function, without changes in DNA base sequence
What is methylation?
- methyl group attaches to cytosine (sometimes adenine)
- if promoter region methylated, transcription factor cannot bind so transcription prevented (mutation)
- so gene not expressed as DNA wound up
- so protein not produced that prevents cell division = no control of mitosis
- increased methylation = decreased gene expression
What is acetylation?
- acetyl group added to lysine (amino acid) found within histones
- reduces attraction of - charged DNA backbone to histone
- DNA less condensed so transcription machinery can access DNA
- increased acetylation = increased gene expression
Define epigenome
chemical groups on DNA molecule that cause it to wind/unwind in response to environmental factors e.g age, stress, pollution
BUT DNA base sequence unchanged
How is a stem cell produced
- zygote + blastocyst (very early embryo)
- embryonic stem cells removed from inner cell mass
- grown in culture in lab (fluid w/ nutrients) to grow more cells
Examples of stem cell therapies
- spinal cord injuries
- heart disease
- organ transplants
- bladder conditions
- respiratory diseases (donated windpipes)
4 mechanisms that control gene expression
- transcriptional regulation
- post-transcriptional regulation
- translational regulation
- post-translational regulation
How can transcription of a particular gene be controlled?
- all transcription factors must combine and form Transcription Initiation Complex (TIC)
- specific TIC controls transcription of particular gene
What are transcription factors?
- regulatory proteins (complex with different subunits) which can cross cell and nuclear membranes
- lipid-soluble
- can be activators/repressors
- DNA binding sites specific to base sequence in promoter region of complementary gene
How do inhibitory transcription factors work?
- bind to and neutralise stimulatory transcription factor subunit
- OR bind to TIC and prevent it becoming complete and active
1st mechanism
- water soluble hormones act by 2nd messengers e.g insulin
- lipid soluble hormones act directly e.g oestrogen
RNA interference (RNAi)
- occurs in cytoplasm
- post-transcriptional
Describe the process of RNA interference
- double stranded RNA (dsRNA) hydrolysed to siRNA
- siRNA binds to protein complexes in cytoplasm
- use energy from ATP hydrolysis to separate 2 siRNA strands, exposing nucleotide bases
- single-stranded siRNA binds to target mRNA via complementary base pairing
- mRNA cut into fragments by another enzyme
- mRNA can’t be translated so no protein production
- fragments broken down into RNA nucleotides by enzymes
What does micro RNA (miRNA) do? (type of RNAi)
targets multiple mRNA molecules
Describe main characteristics of benign tumours
- slow growth
- very large growth but can’t spread
- compresses tissues, preventing blood flow and nerve impulses
Why does mitosis not happen all the time?
cell cycle controlled
Describe main characteristics of malignant tumours
- fast growth
- spread through blood/lymph (metastasis) and invade surrounding tissues
- cancerous; ‘steal’ nutrients from healthy cell, causing surrounding cell death
Define tumour
abnormal mass of cells
Define apoptosis
cells self-destruct to ensure they don’t divide
Features of tumour suppressor genes
- slow cell division
- stimulate apoptosis
(loss of these allows cancer)
Features of proto-oncogenes
- stimulate cell division
- inhibit differentiation
- halt cell death
- mutated version: oncogenes (cancerous, can be 1 or more)
What do oncogenes do?
- increase cell’s continual growth and division
- decrease differentiation
- decrease apoptosis
Describe the process of hypermethylation
- tumour suppressor genes inactivated
- decreased transcription
- increased cell division and tumour formation
e.g BRCA1 gene (breast cancer)
Describe the process of hypomethylation
- occurs in oncogenes, activating them
- forming tumour
Why might an individual who inherits increased risk of developing cancer not have it?
- often born w/ 1 defective copy of tumour suppressor gene
- 2 defective copies lead to cancer
- unless 2nd copy mutates, person has a functional copy of the gene
Define promoter region
DNA section upstream from coding region that is protein binding site for gene expression
e.g RNA polymerase during transcription
Which epigenetic factors result in tumour development?
- tumour suppressor genes + oncogenes, and the abnormal methylation of these
- increased oestrogen concentrations in the development of some breast cancers
