Disorders of cell growth Flashcards
cell cycle phases
Interphase G1G2G3, Mitosis, Cytokinesis
cell cycle control measures
phases must be in correct sequence, DNA synthesis and mitosis must occur correctly, daughter cell must receive full chromosome complement, mutations must not pass on
checkpoints of cell cycle
G1/ S restriction point and G2/M checkpoint
what is checked at G1 point
nutrient supply, external stimulus (hormones, growth factors, cytokines), cell size, DNA damage
what is checked at G2 point
cell size, DNA damage
what is checked at S phase point
DNA replication
What is checked at M phase point
chromosome alignment
cell cycle dependent enzyme
CDKs - needs cyclin to be active. when active they phosphorylate the target proteins and orchestrate entry into next phase
cell cycle inhibitors
CIP/KIP family `(p21,p27), INK4a family (p16)
retinoblastoma protein
when hypophosphorylated state, the pRB is active and suppresses tumours. mutations in Rb favour proliferation
carcinogenesis
failure of cell cycle control- mutations in genes regulating cell division, apoptosis, DNA repair cause loss of control of proliferation
two frequently disrupted pathways
cyclin D-pRB-E2F pathway, p53 pathway
p53
promotes gene repair at G1 or apoptosis if the gene repair fails. if p53 mutated then genetically damaged cells proliferate
cyclin D-pRB-E2F pathway
pathway controls the G1/S transition of the cell cycle by positive and negative regulation of E2F-responsive genes required for DNA replication.
carcinogenesis is caused by
oncogenic viruses, inherited factors (5-10%), genotoxins- cause irreversible genetic damage or mutations through chemicals or radiation
why does inherited retinoblastoma not always show up in individuals with the inherited gene
multiple hits to DNA are necessary to cause cancer. need more than one hit for the tumour to develop
anti-oncogenes
tumor suppressor genes that function to retrain inappropriate cell growth and also stimulate cell death- p16, cyclin D, CDK4, Rb
most common types of cancer that can be genetically transmitted
breast, colorectal, gynaecologic, endocrine
porto-oncogenes
normal genes coding for normal growth regulating proteins
oncogenes
cancer causing genes- activated by alteration of photo-oncogene structure or dysregulation of expression
process of chemical carcinogenesis
DNA bases react with chemical carcinogens and form covalently bound products called DNA adducts. this can lead to activation of oncogenes and loss of anti oncogenes
how does radiation affect cells
target DNA bases and damage them
how do oncoviruses work
virus genome inserts near a host protooncogene which causes over expression of protooncogene or virus directly inserts into and oncogene causing cell division
types of virus that cause cancer
HPV (genital, throat, anal), hep B(liver) , EBV (lymphoma)