cell cycle and tumor stem cells Flashcards
Cdks
cyclin dependant kinases, swiching in cell cycle, can phosphorylate but in complex with cyclin only
cyclin
protein important in cell cycle
E2F
NTF, resent at the promotor of the MYC gene and inhibited by RB, If cells want to enter S phase they have to relieve the RB/E2F interaction
3 ways to release RB form E2F
+ Inactivating mutations in RB (irreversible)
+ binding by a DNA tumor virus oncogene
‐ Adenovirus E1A, SV40 large T, papillomavirus E7: all bind RB and release it from
binding to E2F (irreversible)
+ during cell cycle reversible: phosphorylation (Serine/threonine) of RB by cyclin/Cdk‐
complexes
phosphorylation of RB
when transcription factors FOS and JUN are activated they will induce the expression of cyclin genes and Cdks and they will form a complex which will phosphorylate RB. RB loses its connection to E2F. Now E2F can work as a transcription factor for the s fase genes such as MYC.
cdki
cyclin dependant kinase inhibitor protein, stops or delays the progression of the cell cycle,
Cdki INK and CIP activation
inhibit phosphorylating of RB, TGFB induces signaling pathway (via SMADS) that results in increased expression,cell cycle stopped in GO, p53 upon binding results in increased expression of cdki’s, stops in G1
INK4A
activated by TGFB stimulation, codes for ARF, 2 proteins encoded on same locus
ARF
activated p53 which induces aptosis
darwinian system
continuously select for cells with growth advantage in th available environment
MuTaTo
after identification of cancer cell surface receptors use a panel of peptides that bind these receptors and couple these to a toxin that kills the cells, only succes in mice
tumor cell characteristics
- can infect organism when transplanted
- unlimited poliferation potential
- autonomous growth - make their own growth factors, activating RAS
- abnormal karyotype
5.mutations in oncogenes and tumor supressor genes - multidrug resitance
- anchorage independant growth
- loss of contact inhibition
autocrine growth
tumor cells make their own growth factors
stem cells properties
indefinite lifespan, durg resistance, anchorage independant, divide slow
neuroblastoma
neuroblast, prefer the cell cycle but can still differentiate, treatment results in differntiated neuron, only present in kids
niche
local environment that allows them to slowly divide and release off spring for differentiation
transit amplifying cell
fast dividing but not fully differentiated cells, can turn cancerous?
ETM
epithelial mesenchymal transition, epithelial cells change into mesenchymal cells, resemble stem cells but not epithelial cells in which the mutation occured, differentiated cell converted into cancer cell, fits IPP model
features of cancer cells not explained by stem cell theory
‐ Many mutations and chromosomal changes in tumor cells (how can this happen
without progression phase)
‐ After treatment the cancer can relapse in resistant form
‐ Stem cells divide infrequent; tumor cells divide frequent
‐ Cancer stem cells hypothesis does not allow reversibility (epithelial‐mesenchymal
transition)
consequences cancer stem cell treatment
‐ Current therapy mainly aimed at fast dividing cells
‐ Cancer stem cells are multidrug resistant
‐ When antitumor drug does not eliminate the cancer stem cells the tumor grows
back: you need to target the stem cell
‐ You can target/inactivate the stem cell niche: cancer stem cell lose self‐renewal
and differentiates
