Week 3 - Lecture 1 - Altered Cellular Proliferation and Differentiation Flashcards
cancer definitions
is a chronic disease characterised by remission and relapse
arises from uncontrolled proliferation of cells that have the ability to spread to other parts of the body and continue to grow
derived from greek word for crab, Karkinos (carcinoma)
cancer is a malignant tumour ( they can spread to other parts of the body)
a benign tumour is not malignant and cannot spread (but is still uncontrolled proliferation of cells)
tumours are also referred to as a neoplasm - new growth
not all tumours or neoplasms are cancerous (some are benign)
Cell proliferation
process of increasing cell numbers- generation of new daughter cells
normal tissue : regulated process
- actively dividing equivalent of number of dying/shed
- injury increases cell production
humans have 2 major categories of cells
gametes and somatic cells
-gametes : meiosis
-somatic cells : mitosis
in terms of proliferation
- the 200 cell types in our body are divided into 3 large groups
- the undifferentiated stem cells that be triggered to enter cell division when needed
- progenitor or parent cells that continue to divide and reproduce (blood, skin)
- Well differentiated or rarely dividing cells (neurones, cardiac and skeletal muscle)
cell differentiation
the process whereby proliferating cells becomes progressively more specialised cells types
the endpoint is fully differentiated adult cell with
- specific structure
- specific function
- specific life expectancy
- RBC is terminally differentiated : concave, oxygen carrier, lifespan of 120 days
differentiation occur under the direction genes growth factors nutrients environmental stimulation
Stem cells
highly undifferentiated
potential to divide into progenitor cells (produce more functional cells) or stem cells (produce more of themselves)
progenitor can divide further and differentiate
single stem cell can give rise to the many cells needed
once they are terminally differentiated they have a reduced mitotic rate
normal cell
grow, divide and differentiate
aware of their neighbours and curb their growth to accommodate the m
monitor their own growth
respond to their environment
do not divide when they have damaged genetic information
die when required (too old or damage beyond repair)
carcinogenesis
the origin and development of cancerous neoplasm
neoplasms : irreversible and deviant cellular development (out of control cell proliferation)
cancer : highly invasive and destructive neoplasms (they are malignant as they can spread to other parts of the body )
-cancer cells do not reopens to our body’s normal regulation of cellular proliferation and differentiation
- can develop from almost all cell types including
- proliferating parenchymal (functional) tissue/organ
- proliferating stromal (supportive) cells
- labile cells (i.e. epithelial cells, blood cells) are highly prone to neoplasm development
- cancers in permanent (undividing) cells (neurons, mature cardiac cells) are less common
what makes a cancer cell
normal cells are not immortal. In fact, your cells are only designed to divide up to 80 times before going into a permanent cell arrest. Cancers overcome this to have infinite divisions (immortality)
when our DNA is damaged, if it cannot be repaired then it will undergo apoptosis
Some cancer cells produce and secrete certain proteins to become invisible to our immune system
normal cells require close proximity to the vascular system to survive. Neoplasms cannot grow bigger than 10mm without producing proteins that encourage the growth of new blood vessels to the tumour (angiogenesis)
normal cells are usually in contact with other similar cells to form a tissue. Cancers learn to break away from their adjacent cells, invade into the blood/lymphatic system and grow in other locations
Genetics basis of cancer
cancer arises through genetic mutations to active/inactive pathways (see previous slide for some examples of pathways)
Multiple pathways are required to be altered for a cancer to develop
genetic mutation example
acquired (after birth) : exposure to mutagens, spontaneous (somatic cancers)
inherent in the germline (before brith) : passed from parent to children (familial cancers)
- inherited predisposition : high risk of developing cancer
Exposure to mutagens, spontaneous mutation
if the mutation occurs in somatic cells, it is not passed to the offspring
if the mutation occurs in germline cells, It can be passed to future generations
cancer is a dysfunction of our genes, so what genes are normally altered in cancer
oncogenes
tumour suppressor genes
Oncogenes
cancer gene
these genes in a normal (Non-mutated) state are called proto-oncogenes and their role is to promote protein synthesis and cellular growth when required
we have observed many cancers mutate these proto-oncogenes to aberrantly increase their activity (i.e. turn them on) resulting in
- promote unregulated cell growth
- inhibition of apoptosis (programmed cell death)
activation : porto-oncogenes (normal gene) become oncogenes
Altered genes leading to cancer: oncogenes
proto-oncogenes are normal genes
have viral role in regulating cell function
cancer just exploits our current tools for cell proliferation
activated through 1 of 3 ways
- point mutations
- translocation
- gene amplification
point mutation
single nucleotide base damage/mutation
may lea to increased functional activity (if the DNA mutation results in a change in the protein) or increased gene expression (eg. the mutation Is in the gene promoter)
- spontaneous (error in DNA replication during S phase )
- exposure to environmental influences
- carcinogenic chemicals
- radiation
translocation
chromosome breaks, relocates and united with one another
produces a brand new protein (encoded partly from two different chromosomes) called a fusion protein. This new fusion protein will function like an oncogene
cells deviates from expected growth and differentiation states
occurs in blood cancers (leukaemia, lymphoma )
and some solid tumours (eg. bone and fat cancers)
