Wednesday, March 14, 2012

Gene can both prevent and promote cancer

Cancer is primarily a disease of the DNA, as cells need their genomes modified in order to acquire the capability for malicious growth. Our genetic code, which consists of thousands of individual genes, is used as a blueprint for the production of proteins that together perform all of the body's functions. When the blueprint is modified, several proteins can either be disabled, or increased in activity. Cells need a mixture of inactivated proteins and more highly active proteins in order to become cancerous. This is because some of them protect against cancer development, while others can increase uncontrolled growth if they become more active. However, one gene appears to be surprisingly ambiguous, as it can protect against tumours, but also aid in cancer development.

Research from the Spanish National Cancer Research Centre revealed that a gene called Chk1 promotes the development of tumours. However, this particular gene was already known as a tumour-suppressor, and thus beneficial to prevent cancer. The scientists think Chk1 performs this dual function because cancer cells have a way of using its protective features in order to keep themselves alive. A devious trick to abuse the body's protection mechanisms, but for us it is important knowledge in understanding tumour physiology.

Chk1 is what we call a 'guardian of the genome': it protects our genetic code against damage caused by mutations or DNA damage. It makes sure the genome is intact before cells undertake activities such as replication of the DNA in order to create daughter cells. Because it can halt the normal cell cycle, it protects against uncontrolled growth caused by mutated genes that are no longer able to control the cell. Chk1 is not the only protective protein in the body: P53 has similar features, and is probably the most well-known 'guardian of the genome'. With P53 intact, cancer rarely sees the chance to develop itself, and most tumours are marked by inactivated or dysfunctional P53.

At the Spanish National Cancer Research Centre, scientists genetically modified mice to have an extra set of a Chk1-producing gene. What they found is that it boosts the capability of cancer to manifest itself. This happens because cancer-promoting genes cause genetic instability in tumour cells: normally this is favourable for them because it allows for accumulation of the necessary mutations in order to become cancerous, but it also makes them more susceptible and prone to die from the sustained damage. Apparently, when Chk1 is active in cancer cells, it does exactly the opposite from what it was originally supposed to do. It no longer aids in keeping cells healthy, but it keeps the tumour alive by preventing cell death induced by DNA damage.

Normally, cancer is genetically described as the loss of protective genes, while so-called oncogenes get the chance to promote uncontrolled growth. The present study reveals a protective gene showing two sides of the same coin. Tumours make handy use of the protective tools provided by the cell: in many types of cancer Chk1 is found to be overexpressed. The dual role of protective genes aids us in further unravelling tumour physiology and finding their weak spots.
A circle displaying the cell cycle. After dividing (M), the cell needs to grow (G1) before it can divide again. It can also go into a rest phase (G0) which halts the cycle. After the G1 phase, cell need to create an extra set of blueprints for the daughter cell, so they copy their DNA(S). It is followed by another intermittent phase (G2) after which division (M) takes place and the cycle repeats. This can also be summed up as division (M) followed by a long interphase (I) after which division repeats. Every step in the cycle has checkpoints, which is where the 'guardians of the genome' come in.

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