CancerQuest | Cancer cells are addicted to oncogenes.

This is the first in a series of featured articles that have been chosen to highlight key aspects of cancer biology and treatment. These articles may be older but they clearly present the defining 'Hallmarks of cancer'.

In this research, mice were genetically engineered to produce too much of two different oncogenes. The first is MYC, a transcription factor that drives cell division forward. To control the types of cancer arising in the mice, the researchers created a version of the MYC genet that would only be active in B lymphocytes (B cells). The second gene is BCL-2, a member of a large group of genes that produce proteins which block (apoptosis). Apoptosis is a normal response in cells that have been damaged (i.e. by chemicals or radiation) or are behaving abnormally (i.e. cancer cells).

In this model system, the production of Bcl-2 protein was controlled by the researchers and could be turned off by the addition of a chemical to the drinking water of the animals. When both genes (MYC and BCL-2) were active, the animals rapidly developed a B-cell leukemia. When the BCL-2 gene was turned off, the leukemia cells disappeared and the mice were 'cured' of their cancer.

The results strongly support the idea that cancer cells are 'addicted' to the oncogenes that helped them develop. Other research from many groups and in different systems supports this model.

Bottom Line: Cancer develops as a result of accumulated mutations in tumor suppressor genes and oncogenes. It is possible that once cancer has developed, the activity of the oncogene that began the process is no longer necessary. This research, in a mouse model of leukemia, demonstrates that the cancer cells remain 'addicted' to the oncogenes.

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Original Article: Letai A, Sarcinelli M, Beard C, Korsmeyer S. Antiapoptotic BCL-2 is required for maintenance of a model leukemia. 2004. Cancer Cell. Sep;6(3):241-9.