Cancer Cell Biology Flashcards
What is cancer?
A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can spread to other parts of the body through the blood and lymph systems.
What are the causes of cancer?
- Environmental/ lifestyle factors
- Infectious agents - HPV (cervical)
- Environmental carcinogens – smoking (lung)
- Diet – alcohol
- Genetics
- Inherited – BRCA in breast cancer
- Somatic - RAS in pancreatic cancer
What are proto-oncogenes?
a gene that when mutated/over-expressed contributes to the dev of cancer
What are oncogenes?
- a gene that contributes to the dev of cancer
- has diff mutation to proto-oncogene so protein made differs from normal protein made in cells
Why do oncogenes cause cancer when protooncogenes do not? Describe 4 mechanisms
Oncogenes result in the enhanced activity of the encoded protein
- Activating mutations e.g. Ras(G12V)
- Overexpression through promoter exchange: more protein prod than normal e.g. Bcl 2 protects cells from apoptosis which gives cell survival adv
- Can also get protein prod that’s not part of normal biology through gene fusion so no mech to regulate its activity –> enhanced activation e.g. BCL ABL drives prolif
- Elevated expression through gene amplification e.g. EGFR on surface of breast cancer cells which ↑
signal to div + prolif
Why is RAS significant?
RAS protein part of mech of cell div – RAS mutation means protein always on
What is a tumor suppressor gene and what are they known as?
a gene whose loss contributes to the
development of cancer
Tumour suppressor gene have therefore been classified as “gatekeepers” and “caretakers”
How do mutations affect oncogenes?
A mutation in a single allele
can result in deregulation of
signalling
How do mutations affect TSG?
A mutation in a single allele is insufficient to disrupt protein function*
Loss of both alleles is usually required to disrupt tumour suppressor function
What is the cell cycle + the phases?
the interval between successive mitoses
Divided into 2 phases, interphase (I) and mitosis (M)
Interphase further divided into G1, S and G2 phases
How do cancer cells differ in the cell cycle vs normal cells?
Cancer cells spend most of their time in cell cycles due to loss of regulatory control, most cells don’t (in G0)
List the 3 main control points
• In G1 – decision to enter S phase
End of G2 – decision to enter M phase
• Progression through M
What provides signal to go from G1 to S phase?
Growth factor signalling is signal to go from G1 to S
GF outside cell bind to receptor à initiates receptor signalling pathway ∴ ends up with signal to go from G1 to S phase
What is RB and how can its loss cause tumor suppression?
Rb protein is a major cell cycle regulator
Retinoblastoma sits on DNA + prevents transcription of genes for kinases that cell needs to go further into cell cycle
When GF binds to receptor on cell –> protein phos –>
∴ can’t bind to E2F –> protein falls off –> transcription of early cell cycle genes that allows cell to transition into S phase to enter cell cycle
RB is tumor suppressor ∴ loss can drive tumor suppression
Cell senses that its going to cell cycle to often + ∴
triggers apoptotic pathways
When is apoptosis induced and how?
in response to DNA damage OR oncogene activation
• Mediated by p53
