10.4 Cancer and the Cell Cycle

By the end of this section, you will be able to explain how cancer is caused by uncontrollable cell growth and how normal cell genes become oncogenes.

Errors do occur despite the redundant levels of cell-cycle control.
The cell-cycle checkpoint surveillance mechanism monitors the proper replication of DNA during the S phase.
When the cell-cycle controls are fully functional, a small percentage of replication errors will be passed on to the daughter cells.
If there is a coding portion of a gene that is not corrected, there will be a genetic change.
A faultyprotein that plays a key role in cell reproduction is the cause of all cancer.

There may be a slight delay in the binding of Cdk to cyclin or an Rb protein that detaches from its target DNA while still phosphorylated.

Minor mistakes may allow subsequent mistakes to occur more easily.
Small uncorrected errors are passed from the parent cell to the daughter cells and amplified as each generation produces more non-functional proteins from uncorrected DNA damage.

As the effectiveness of the control and repair mechanisms decreases, the pace of the cell cycle increases.

Consider what might happen to a cell with a recently acquired oncogene.
Alteration of the DNA sequence will result in a less functional or non-functional protein.
The result is detrimental to the cell and will likely prevent the cell from completing the cycle; however, the organism is not harmed because the mutation will not be carried forward.
The damage is minimal if a cell cannot reproduce.
A change in a genes activity can increase the activity of a positive regulator.
The cell cycle could be pushed past a checkpoint before all of the required conditions are met, if there is a mutation that allows Cdk to be activated without being partners with cyclin.
If the daughter cells are too damaged to undergo further cell divisions, there would be no harm to the organisms.
If the atypical daughter cells are able to undergo further cell divisions, subsequent generations of cells may accumulate even more mutations, possibly in additional genes that regulate the cell cycle.

Anyprotein that influences the cycle can be altered in such a way as to override the cell-cycle checkpoint.
When an oncogene is altered, it leads to an increase in the rate of cell-cycle progression.

Many of the negative cell-cycle regulatory proteins were found in cells that had become cancer.

The function of Rb, p53, and p21 is to put up a roadblock to cell-cycle progression until certain events are completed.

If there is a problem, a cell that carries a negative regulator might not be able to stop the cell cycle.

The multiple roles that the p53 protein plays at the G1 checkpoint is not surprising.
A cell with a faulty p53 may fail to detect errors.
The p53 may not be able to signal the necessary DNA repair enzymes even if it is partially functional.
The damaged DNA will remain uncorrected.
At this point, a functional p53 will deem the cell unsalvageable and cause programmed cell death.
There is a damaged version of p53 found in cancer cells.

Hypoxia is a condition of reduced oxygen supply and normal p53 is used to monitor it.

There is no effective block on Cdk activation if the levels of p21 are not adequate.

Without a fully functional p53, the G1 checkpoint is severely compromised and the cell proceeds directly from G1 to S regardless of internal and external conditions.
Two daughter cells are produced when the shortened cell cycle is over.
The daughter cells are likely to have acquired more than one faulty tumor-suppressor gene because of the non-optimal conditions under which the parent cell reproduced.
These daughter cells accumulate both oncogenes and non-functional tumor-suppressor genes quickly.
The result is tumor growth.