Trumpity-Trump!

Trumpity Trump!Interesting story on the BBC today.  Apparently, elephants are less likely to get cancer than humans!  This story is based on the results of this study, which examined cancer rates in a variety of species.  They found that, while in humans the overall risk of contracting cancer is 11-25%, in elephants it is only 5%.  Now, this could be considered surprising, considering what I have previously told you about the common risk factors associated with cancer.

Back in Chinese Whispers, I mentioned that cancer is regarded as an age-related condition – the older you live, the bigger the risk of getting the disease.  Also, in No Bootees, I explained that cancer is caused by an imbalance in growth signals and, in my last post, I spoke about the observation that tall people are more likely to get cancer than short people, possibly because they make more growth signals.  Now if you take all this together, you would expect that the older and bigger something is, the bigger the risk of cancer.  But elephants are much, much bigger than us, and they also have pretty long life spans.  So why is their risk of cancer so much lower than ours……?

Now, obviously, elephants live (primarily) in the wild, so it could be that the lower incidence of cancer is simply due to the fact that they are dying of other things – poaching, disease, poor nutrition etc. – but, even after the research team had put controls in place to account for these possibilities, the risk of cancer was still much lower in elephants.

To try and find out why, the researchers had a look at the elephant genome and compared it to the human version, to look for differences in genes that are known to be related to cancer.  And they found something interesting.  While the human genome contains one single copy of a certain gene called p53, the elephant genome contains up to twenty copies! Now, why is this important?

Back in No Bootees, I described how your body is constantly replacing old, dead cells, by modulating the levels of growth factors to make new ones.  So, your cells will produce factors that encourage cells to grow and divide (Go! signals) and then switches the system off after the dead cells have been replaced, by making factors that prevent growth and division (Stop! signals).  Well. p53, the gene that is multiplied in elephants, is a Stop! signal.  More than that, it is THE Stop! signal!  There are genes which can induce cancer (called “oncogenes”) and there are genes which can prevent cancer forming (called “anti-oncogenes”).  And the most important anti-oncogene we know of is p53.

p53 has many functions, and all of them help to prevent cancer.  The three most important roles it plays are in DNA Repair, Cell Cycle Arrest and Apoptosis.

One of the reasons why cancers can begin is gene mutation, which is where the DNA that makes up your genes gets altered.  If your DNA becomes damaged, then this can be dangerous, because if it isn’t repaired properly, you will end up with mistakes in the DNA, which can change how the gene works.  If this happens inside a gene which controls cell growth, the upshot can be increased Go! signals and this can lead to cancer.  So, the cell will attempt to repair any DNA damage which occurs, and p53 is one of the signals that helps to activate the repair process.  And the first thing it does is shout “STOP!”  This makes the cells freeze where they are and therefore stops the cells dividing in two.  The process of cell division is called the Cell Cycle, so stopping this process is Cell Cycle Arrest.  So, there we have two of the main functions of p53.  It stops the cells dividing and helps initiate DNA repair, both of which can help prevent the normal cell from changing into a cancer cell.

And then we come to p53’s other main function.  Apoptosis.

We scientists love our high-falutin’ words, and “Apoptosis” is a doozy, isn’t it?  The word comes from the ancient Greek words for “separate “ and “fall” and the word “apoptosis” was originally used to describe the way that leaves die and fall off of trees in Autumn.  And that gives an idea of what the word means in a cellular biology setting, that cells will decide to die, when the time is right.  So, another (less fancy) way of saying Apoptosis is “Programmed Cell Death”.  What happens is, if a cell detects an imbalance in the growth signals – too many Go! or not enough Stop! – the cell will try to correct the imbalance.  But….what if the cell can’t fix it?  What happens then?  Well, as a last resort, the cell will initiate a Self Destruct mechanism, to stop itself turning into a cancer cell.  And so, the dodgy cell kills itself and the potential crisis (ie. cancer) is prevented.  Apoptosis is the name given to the Self Destruct mechanism.  And p53, the gene that is multiplied in elephants, is a control switch for this process.

This is why the  researchers say that elephants have reduced risk of cancer.  The higher levels of p53 mean that you would expect their cells to have increased activation of DNA damage repair processes, increased arrest of cell growth in response to DNA damage and increased levels of Apoptosis.  And, indeed, the research team found all of these in elephant cells.

Now for the big question: How does all of this help us?  Answer:  It doesn’t.

Sorry.

While the fact that elephants have increased levels of p53 wasn’t known before, p53 itself has been known about for a looooong time.  There has been a helluva lot of research into the function of p53 – research which is ongoing.  So, this isn’t new.  But the big problem is this: everything I’ve said about p53 describes what it does in normal cells to prevent cancer.  But, obviously, cancers exist.  So, how can that happen, if p53 is so good at stopping it?  The answer is both obvious and deeply depressing.  In the majority of cases of cancer, p53 is missing.  It is either mutated (ie. altered so it doesn’t work), or it is switched off.  In one sense, that is how cancers happen in the first place.  If a cell is damaged, or has an imbalance of Go! signals, then p53 activates and stops it becoming cancerous.  But if, inside these cells, p53 is also damaged, then these protective mechanisms don’t work and there is nothing to stop the cancer beginning.  And that is what all of the research into p53 has been trying to do – to try and either replace the missing/faulty p53, or to try and “kick-start” the p53 response in cancer cells, in order to try and turn the cancer cell back into a normal cell.

So, while the fact that elephants have more p53 than us is interesting, it isn’t going to help us stop human cancers anytime soon.  And it may not be the whole reason why elephants get cancer less than us anyway. As Prof Mel Greaves from the Institute of Cancer Research in London explains, there are plenty of other reasons why the cancer risk in humans is so high:

“You’ve never seen an elephant smoke!”

Abegglen, L., Caulin, A., Chan, A., Lee, K., Robinson, R., Campbell, M., Kiso, W., Schmitt, D., Waddell, P., Bhaskara, S., Jensen, S., Maley, C., & Schiffman, J. (2015). Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans JAMA DOI: 10.1001/jama.2015.13134

ResearchBlogging.org

AG McCluskey (2015). Trumpity-Trump! Zongo’s Cancer Diaries

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