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Author Topic: How can hematopoietic stem cells become cancerous if their p53 gene is intact?  (Read 2018 times)

Offline rebpalma

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Hi! First-time poster here. I'm a mathematician with a keen interest in biology and cancer research. I'm studying biology at home, as I work and I can't compatibilize my schedule with that of a university student. But I have many questions and no one to ask them to. Could you please help me? Is this the place to do this?

My first question is regarding Chronic Lymphocytic Leukemia (of B-cells) although it may apply to other types of cancer. In CLL, patients may or may not show a deletion of the p53 gene. I've read that the p53 gene produces the p53 protein, which acts as a quality controller for the right replication of cells. More specifically, I believe the p53 protein checks that the duplication of the DNA has been made correctly after the synthesis subphase of the interphase.

My question is, how is it possible that patients with functioning p53 proteins in their B-cells ever developed leukemia? Shouldn't have the p53 proteins forced all the cancerous cells to commit suicide?

Thank you very much in advance for your answers!


 

Offline schneebfloob

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Cancers have no single cause. There are certain key mutations within certain genes that make cancer far more likely, and P53 is one of those genes. Inactivation or disruption of P53 alone probably won't trigger cancer, but can certainly contribute to it. The cell has multiple different failsafes, such that a single mutation can't cause cancer in itself. For example, p53 may still be being produced, but fundamentally it's part of a signalling pathway. This pathway can trigger DNA repair or in the worst case apoptosis, or programmed cell death. If there are mutations that prevent the other components in that pathway from being produced, or prevent them from responding to p53, then p53 will be useless and the cell may be able to proliferate despite the damage.
« Last Edit: 04/08/2012 17:22:40 by schneebfloob »
 

Offline rebpalma

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Thank you schneebfloob, you explanation is very clear!
 

Offline schneebfloob

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You're welcome :) It's a very interesting topic! Unfortunately, I don't know very much about CLL specifically, but the principles are pretty much the same.

Perhaps a good example would be EGFR signalling (because I know more about it  ;)). EGF binds to EGFR (Epidermal Growth Factor Receptor), and can trigger a number of different pathways that result in cell proliferation, growth etc. These pathways are implicated in lots of cancers because of this. You can get mutations in EGFR that mean that it's always switched on, or mutations that cause the cell to produce EGF itself (so it keeps EGFR activated by itself), or you can get over-expression of EGFR so the cell receives more "pro-growth signals". All of these things are bad, and will contribute to cancer but are kept in check by certain failsafes. Eg EGFR may be ubiquitylated, which is how the cell marks proteins for degradation. This will keep the pro-growth signals in check. But, there are mutations that can block or impair the ubiquitlyation, or enable it to be bypassed in some way.

I hope this helps. Cancer isn't so much about one root cause, but a combination of different mutations and factors that enable the cell to bypass the failsafes. The cell needs to accumulate different mutations to allow growth, block apoptosis, free itself from its surroundings if it's to metastatise, and perhaps recruit blood vessels to provide itself with oxygen. It's a very complex process with lots of different mutations that can contribute to tumourigenesis.
« Last Edit: 04/08/2012 17:27:12 by schneebfloob »
 

Offline rebpalma

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Thanks again!
 

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