6.3 Cancer and the Cell Cycle
Learning Objectives
By the end of this section, you will be able to:
- Explain how cancer is caused by uncontrolled cell division
- Understand how proto-oncogenes are normal cell genes that, when mutated, become oncogenes
- Describe how tumor suppressors function to stop the cell cycle until certain events are completed
- Explain how mutant tumor suppressors cause cancer
Cancer is a collective name for many different diseases caused by a common mechanism: uncontrolled cell division. Despite the redundancy and overlapping levels of cell-cycle control, errors occur. One of the critical processes monitored by the cell-cycle checkpoint surveillance mechanism is the proper replication of DNA during the S phase. Even when all of the cell-cycle controls are fully functional, a small percentage of replication errors (mutations) will be passed on to the daughter cells. If one of these changes to the DNA nucleotide sequence occurs within a gene, a gene mutation results. All cancers begin when a gene mutation gives rise to a faulty protein that participates in the process of cell reproduction. The change in the cell that results from the malformed protein may be minor. Even minor mistakes, however, may allow subsequent mistakes to occur more readily. Over and over, small, uncorrected errors are passed from parent cell to daughter cells and accumulate as each generation of cells produces more non-functional proteins from uncorrected DNA damage. Eventually, the pace of the cell cycle speeds up as the effectiveness of the control and repair mechanisms decreases. Uncontrolled growth of the mutated cells outpaces the growth of normal cells in the area, and a tumor can result.
Proto-oncogenes
The genes that code for the positive cell-cycle regulators are called proto-oncogenes. Proto-oncogenes are normal genes that, when mutated, become oncogenes—genes that cause a cell to become cancerous. Consider what might happen to the cell cycle in a cell with a recently acquired oncogene. In most instances, the 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 cell cycle; however, the organism is not harmed because the mutation will not be carried forward. If a cell cannot reproduce, the mutation is not propagated and the damage is minimal. Occasionally, however, a gene mutation causes a change that increases the activity of a positive regulator. For example, a mutation that allows Cdk, a protein involved in cell-cycle regulation, to be activated before it should be could push the cell cycle past a checkpoint before all of the required conditions are met. If the resulting daughter cells are too damaged to undertake further cell divisions, the mutation would not be propagated and no harm comes to the organism. However, if the atypical daughter cells are able to divide further, the subsequent generation of cells w