Angela's cancer biology, molecular biology Flashcards
Senescence - continued telomere erosion in cells will lead to death in all but immortalized cells. By what mechanism do immortalized cells overcome this?
Through reactivation of telomerase
What is telomerase?
RNA dependent DNA-polymerase that synthesizes telomeric DNA
What are the 2 components of telomerase?
An RNA template and hTERT
hTERT: human telomerase reverse transcriptase
Telomerase consists of two essential components:
1) the functional RNA component (in humans called hTR or hTERC), which serves as a template for telomeric DNA synthesis
2) a catalytic protein (hTERT) with reverse transcriptase activity
What is hTERT?
hTERT: human telomerase reverse transcriptase
a catalytic subunit of the enzyme telomerase, which, together with the telomerase RNA component (TERC), comprises the most important unit of the telomerase complex.
expression of hTERT is repressed after embryogenesis
Mitotic cell cycle , name 5 phases?
GO: rest, not dividing
G1 phase: protein synthesis
S phase: DNA synthesis/replication
G2 phase: growth/prep to divide
Mitosis: chromosomal segregation in mitosis, cell separation in cytokinesis
What is least associated with cancer cells?
Choices:
a. Disjunction
b. Requirements of increased substances for proliferation
c. Contact inhibition
CONTACT INHIBITION
Contact inhibition is a process of arresting cell growth when cells come in contact with each other
Disjunction is the normal separation or moving apart of chromosomes toward opposite poles of the cell during cell division
Where does angiostatin work?
its an angiogenesis inhibitor, direct action against endothelial cells.
Where does FAK work?
focal adhesion kinase (FAK) is a cytoplasmic protein tyrosine kinase that promotes tumor metastasis. Can also act in nucleus
FAK signaling promotes cell motility and invasion and activation of matrix-degrading metalloproteinases, thus stimulating the ability of cells to invade through the ECM.
It is a positive regulator of cell growth by triggering both survival and proliferative signals.
When in the cell cycle are cells diploid?
G1 and G0
When in the cell cycle are cells tetraploid?
G2 and M
The steps of cancer metastasis include:
proliferation
angiogenesis
invasion
embolization or circulation
transportation
adherence at distant organs or vessels
What are cadherins?
transmembrane glycoproteins that mediate cell-cell communication via calcium dependent interactions
Mnemonic: cad- Ca Dependent her -hear (like communication)
What are integrins?
transmembrane glycoproteins that serve as signaling molecules for regulation of apoptosis, gene expression, proliferation
What part of the cell cycle does a labeling index measure?
S phase fraction (proliferating cells)
What percentage of cells in human malignancies are mitotically active?
3-15%
How does a labeling index work?
Uses autoradiography to detect H-thymidine in cellular DNA
A labeling index measures the proportion of cells in a sample of tissue that are producing DNA (#cells in S phase).
What is Flow cytometry used for?
Flow cytometry is used to analyze cell cycle and growth fraction
It can analyze replication states using fluorescent dyes to measure the four distinct phases of the cell cycle. Along with determining cell cycle replication states, the assay can measure cell aneuploidy associated with chromosomal abnormalities.
Which phase of the cell cycle has the highest amount of protein synthesis?
G1
Because it prepares for replication in S
Which type of cells does a labeling index identify?
a. G1
b. S phase
c. G2
d. SM
S phase
When is a cell tetraploid?
G2 - M
When is a cell diploid?
G1
How do you humanize a mouse antibody?
To make it humanized, must graft complementarity-determining region (CDR), the hypervariable domain, that determines specificity, from a mouse antibody onto a human variable region framework, creating humanized antibodies
You can also reduce the immunogenicity of the mouse antibodies using genetic engineering to generate chimeric antibodies containing human constant domains (Fc) and the mouse variable domains (Fv) to retain the specificity
What do proteolysis, angiogenesis, and cell migration have to do with tumor biology?
Proteolysis - proteases synergize to establish an environment that allows tumor cells to thrive, invade into surrounding tissue, and colonize distant organs
Angiogenesis - growth of new blood vessels that tumors need to grow
Migration - occurs during the whole cascade of cancer development and is important during invasion, the initial step of metastasis. Following chemotactic migration, a cancer cell invades into the surrounding tissue and the local vasculature.
What is the role of Rb (retinoblastoma) gene?
Retinoblastoma (RB) is a tumor suppressor known as a master regulator of the cell cycle. It is a transcriptional regulator which interacts with the E2F family of transcription factors and represses cell cycle progression from G2 to M phase.
What is the role of CHK1 and CHK2?
CHK1 and CHK2 are both activated upon DNA damage and can regulate cell division. CHK1 activity has been mostly implicated in the intra-S phase cell cycle checkpoint and the G2–M transition. CHK2 activity is associated with G1–S and G2–M arrests.
