Tumour Pathology 4 Flashcards
What is mitosis?
Mechanism of cellular replication and nuclear division plus cytokinesis.
What results from mitotic division?
Two genetically identical daughter cells.
What is the cell cycle?
The time interval between mitotic divisions.
Why is cell cycle control important?
Must be in correct sequence to produce viable progeny, DNA synthesis and mitosis must occur sequentially, quality control ensures genetic fidelity in daughter cells - each cell must receive full chromosome complement and mutations in DNA sequences must not pass on.
What are external factors in cell cycle control?
Hormones, growth factors, cytokines, stroma
What are intrinsic factors of cell cycle control?
Checkpoints e.g. restriction point (R)
What happens before the restriction point (R)?
Progress before the restriction point through G1 depends on external stimuli, after (R) progression becomes autonomous.
What happens at G0?
It is the resting phase, the cell has left the cycle and has stopped dividing.
What happens at G1 and at the G1 checkpoint?
Cells increase in size and the G1 checkpoint control mechanism ensures everything is ready for DNA synthesis.
What happens at S phase?
DNA replication occurs.
What happens at G2 and at the G2 checkpoint?
Cell grows more, makes proteins and organelles, and begins to reorganize its contents in preparation for mitosis. G2 checkpoint mechanism ensures everything is ready to enter M phase.
What happens at M phase?
Mitosis and cytokinesis - cell growth ceases and cell divides its copied DNA and cytoplasm to make two new cells.
What phases make up interphase?
G1, S and G2
What are the checkpoints?
System of cyclically active and inactive enzymes. A catalytic sub-unit activated by a regulatory sub-unit.
What are the catalytic and regulatory sub-units also known as?
Catalytic sub-units are called cyclin-dependent kinases (CDKs) and the regulatory sub-units are called cyclins.
What is the active enzyme complex?
CDK/cyclin complex
What do CDKs and cyclins do?
Operate at sequential stages of the cell cycle.
What does the active CDK/cyclin complex do?
Active CDK/cyclin complexes phosphorylate target proteins and this phosphorylation results in activation/inactivation of that substrate, the substrate regulates events in the next cycle phase.
What helps regulate the cell cycle?
CDKs, cyclins and CDK-inhibitors.
What causes carcinogenesis?
Carcinogenesis is caused by mutation of genetic material that upsets the normal balance between proliferation and apoptosis.
What causes a cell to lose control of proliferation?
Mutations in genes regulating cell division, apoptosis and DNA repair.
What causes chemical carcinogenesis?
Purine and pyrimidine bases in DNA are critically damaged by various oxidizing and alkylating agents. Chemical carcinogens react with DNA forming covalently bound products called DNA adducts, adduct formation at particular chromosome sites causes cancer.
What causes radiation carcinogenesis?
High-energy radiation if received in sufficient doses e.g. UV, X-rays or gamma radiation.
What is the primary defect in cancer?
Uncontrolled cell proliferation via cell cycle dysregulation.
What are the two regulatory pathways frequently disrupted by cancer?
1) the cyclin D-pRb-E2F pathway
2) the p53 pathway
What is p53’s function?
To maintain genomic integrrity, p53 levels increase in damaged cells (this induces cell cycle arrest at G1 and facilitates DNA repair) and severe damage can mean p53-induced apoptosis.
What happens if p53 is absent or mutated?
There is no G1 arrest, no repair to DNA damage and so genetically damaged cells proliferate and form malignant neoplasms.
