What triggers cell division?

Obviously a key question for cancer, with unchecked cell replication. Is there a factor from outside the cell that enters the cell and triggers division (ie an envioronmental factor), or is it a factor that is already inside the cell.

This assumes that one factor is sufficient, and that there are not multiple factors, any of which could be sufficient. But the issue is not number of factors as much as whether or not the cell wall needs to be crossed by them. Again, the "factor" is something that would be different between normal cells and cancer cells, and would cause that difference.

So, for example, testosterone would not be a candidate answer to this question, because blood contains testosterone, and testosterone goes into toboth both normal prostate cells and into cancer prostate cells.

I think the assumption is that the difference is something that must be "in" the cell, and is passed on to "both?" daughter cells "when" the cancer cell divides.

[Most terminally differentiated cells don't divide, though, I thought.]

11 Replies

  • I have an uninformed answer for you. LOL

    All biological processes are regulated by homeostatic feedback loops. I know of no exceptions to this. Everything is built around DNA and homeostatic feedback loops.

    The apoptosis mechanism is what causes cells to die. My understanding is that cancer is caused by a failure of the apoptosis mechanism.

    Most assuredly there must be another part of this homeostatic feedback loops that causes cells to divide. And no doubt there are many complicated pathways involved. Apparently telomeres are involved in some way.

    Such a basic multi-billion year mechanism has had a long time to evolve all kinds of moving parts to solve all kinds of evolutionary problems.

  • I agree that feedback loops are important, and it is useful to look for the mechanism of the feedback. Saying that all biological processes are regulated by feedback loops seems more like a principle than a fact, since feedback systems can break like anything else can break.

    While cancer cells may live longer that normal cells, i don't think that cancer is a manifestaion of cells living longer, while dividing at the normal rate.

    And if they are dividing normally, then telomeres are not the difference.

    You must be saying that they live longer and divide faster, although telomeres dont control the rate of division, so I dont think that is a good guess, unless it is that cancer cells divide at the same rate but for a longer time, because of telomeres.

  • I have two comments:

    A truly amazing characteristic of a healthy adult organ is that there is no significant variation in organ size. Cell division & cell death is somehow kept in balance. There are situations where the system could break down. Bacterial or viral insult might lead to cell death outstripping cell division. The obligatory response is activation of NF-kB [Nuclear Factor-kappaB].

    NF-kB places a moratorium on cell death. For obvious reasons, NF-kB did not evolve to be chronically activated. Cancer gets around that. NF-kB is an obvious target, since, in addition to inhibition of apoptosis, activation leads to scores of pro-survival genes being transcribed.

    The telomere situation is interesting in cancer. The telomere is a crude cell division count. The telomere system is found in longer-lived species. The only reason for its evolution is to stop fast-dividing cells.

    The risk of an error occurring in cell division seems to be significant. There are correction procedures in place, & suicide provisions if a cell cannot be saved through correction, but with such a huge number of cells undergoing division each day, rogue cells can emerge. The Hayflick Limit means that we cannot live forever. The telomere gets shorter with each division, until division is no longer permitted.

    This is not so with a growing baby. The cells produce an enzyme - telomerase - that allows division to occur with no shortening of the telomere. This is our Achilles heel, since cancer turns the telomerase gene back on. It has to do this, but why is it seemingly so easy?

    To be fair, the system works well, since cancer mostly occurs when men & women are at an age when they could have reared replacements. Evolution cannot improve the health of those who are no longer breeding.

    An exception is the grandmother gene. In the days when a fertile woman was a baby machine, with kids under foot, there would have been a role for a post-menopausal woman. Old men, on the other hand, just sat around & complained that the food wasn't ready. That's why men get PCa - less mouths to feed. LOL But the grandmother gene hypothesis perhaps explains why women live longer.


  • Martin,

    I don't have a specific answer to your question but I have a general one that, I hope, will shed light on the problem.

    Cell division is "regulated" by multiple processes in each of two different ways. Some processes (and there are more than one) promote cell division. Other processes (and there are more than one of those too) restrain or prevent it.

    Specific proteins are involved in each of those two kinds of regulation. Some of them are generic and are found in most kinds of cells and others are specific to particular cell types like prostate cells. The genes that produce the proteins that promote cell division are sometimes called "oncogenes", meaning genes that, when they are "expressed" more than normally (go through the process of generating proteins from the DNA patterns of the gene) can lead to excess cell division and cancer. The genes that produce the proteins that suppress cell division are sometimes called "tumor suppressor genes". If they are functioning properly they can prevent the cell division even when oncogenes are abnormally active.

    As I understand it, more than one DNA mutation is usually required for cancer to occur. There must both be too many attempts at cell division and not enough attempts at blocking it. Sometimes more than one oncogene and more than one tumor suppressor gene must be overly or underly expressed (perhaps because of DNA mutations of those genes, or perhaps by mutations in other genes, see below) before cancer takes off.

    Now, as complicated as that sounds, the true picture is even more complicated because the expression of genes into proteins that regulate cell division are themselves regulated. It is possible for a mutation in some gene to cause a protein to fail to be expressed, or to be overly expressed, or to be non-functional, which in turn cause another gene to be overly or underly expressed or non-functional, which in turn causes an oncogene or tumor suppressor gene to be overly or underly expressed or non-functional.

    And to complicate things even further, there are genes that produce proteins that repair DNA damage. Mutations in those genes can allow damage to other DNA, including DNA for oncogenes and tumor suppressor genes and all of their regulatory genes, to be unrepaired, leading to cancer that becomes more and more aggressive. Damage to DNA is common because of exposure to carcinogens (like tobacco smoke or radiation), because of old age, and because of random accidents that occur when a disorderly soup of chemicals reacts in not entirely predictable ways during cell division. Cells have repair machinery to correct these "errors" and damage to that machinery can make cancer very aggressive indeed.

    There is no intelligent design here. The accidents and vagaries of evolution have produced an astonishingly complicated bag of chemical reactions called a cell, and there are any number of different failures that can occur in cell processes that wind up causing cancer. That is why we say that each person's cancer is different, and why treatments that work well for one patient don't work for another.

    The conversion of cancer from local or benign to metastatic is similarly complex.

    Testosterone and its derivative, dihydrotestosterone, are key molecules in the complicated reactions that lead to prostate cell division. The discovery of that led to the development of the many hormone therapy drugs that slow down or stop the action of the oncogenes. Chemotherapy drugs typically interfere with cell division itself, damaging the proteins or blocking their action in the actual process of mitosis (cell division). They are kind of an artificial replacement for tumor suppressor genes - causing the cell division to go haywire and kill the cell instead of duplicating it. There are undoubtedly many other key molecules that, as we discover their roles and invent ways to manipulate them, will strengthen our ability to fight cancer. And of course, at the same time, very aggressive cancers with rapid mutations often evolve mechanisms to expel, neutralize, or work around the drugs that we use to fight cancer. With billions of cancer cells rapidly dividing and multiplying and undergoing excess numbers of random mutations, it may not take long for one of them to randomly evolve something that stops the action of one of our drugs.

    As has sometimes been said, cancer research makes rocket science look easy.

    I hope what I've said make sense.


  • There are more than one. /or/ There is more than one. ?

    I lean towards "is".

    Yes I do understand that singular is one, and more than one is not singular.

  • I can't say I am a big fan of the idea of "oncogene". Would the gene that codes for the androgen receptor be considered an "oncogene"?

    And I think that most mutations lead to a loss of funtion, rather than an addition of function. True that the function lost might leave a hole that causes a problem, like a missing guard rail.

  • Yes, most mutations lead to a loss of function. Though the effect of losing function can be to increase the rate of cell division.

    Loss of function of a tumor suppressor gene can lead to more frequent cell division than normal. This can happen in various ways. There might be a pathway in mitosis in which a particular protein would normally interrupt, pause or block the division, but the protein doesn't work or never arrives and too many cell divisions occur. There can be mutations that cause multiple copies of an oncogene to be created, increasing the rate of transcription. It has recently been discovered that "extrachromosomal DNA" is sometimes created in tumor cells, and that DNA may include oncogenes that now amplify the number of cell divisions.

    I think all of this incredible, and still not fully understood, biochemical complexity is what makes cancer research so difficult.


  • "increasing the rate of transcription".

    ie increasing protein production is not the same as increasing cell division, and I see no theory as to a mechanism for one causing the other, just assumptions that it does, or may.

    And the word "oncogene" is circular, delusional.

    "I think all of this incredible". I also don't believe it.

    You talk as though an oncogene is a mutation, and one that causes cancer. A mutation causes a loss of function ie causes the production of an onco-protein. What is that protein? If an oncogene is not a mutation, if it is a normal gene, why call it an oncogene?

  • I think my explanation was inadequate, partly due to oversimplification caused by trying to make things simple, and partly due to oversimplification due to the fact that my own understanding is incomplete.

    For clarification I turned to that wonderful fount of wisdom, the Wikipedia. Rather than try to produce a probably inadequate summary of what's there, I'll just refer you to the Wikipedia articles. There's one for "oncogene", one for "tumor suppressor gene", and there are other related articles. Each of them has deeper explanations than I can produce.

    If I understand it correctly, the term "oncogene" doesn't mean that it's a gene that has evolved for the purpose of causing cancer. Rather it's a gene that has evolved for the purpose of aiding cell division and, if upregulated for any reason, can cause too much cell division, which results in cancer. Upregulation can be caused by various kinds of biochemical changes. Some might be caused by mutations in the gene itself; some by changes in genes that promote the expression of the oncogene; some by changes in genes that promote the promoters, or suppress the suppressors of promoters; some by changes that retard the normal degradation of the transcript; some by translocation of the genes to places that are more active or by changes in the cell that cause a gene to be copied so that, instead of, say, two copies of a particular gene promoting transcription, there are now six or ten, and they're all working away.

    I also see too that my use of the term "incredible" gave the wrong impression. It's not that I don't believe these explanations, I do believe them. Rather it's that I think that most of us ordinary non-scientists will find the explanations confusing and hard to understand. It is complicated stuff and, as all cancer researchers know, there can be myriad specific causes for why a cell goes rogue and starts replicating out of control - which is why cancer is so hard to cure.

    Please do read the Wikipedia articles. I think they'll answer your questions better than I can.


  • Martin,

    I will just mention one factor: IGF-I [Insulin-Like Growth Factor-I].

    It is no surprise that milk & milk products are associated with aggressive PCa. Milk is the only food that contatains a growth hormone - bio-identical IGF-I.

    The IGF axis is seriously messed up in PCa, which might explain why elevated insulin in Mets is a PCa risk factor - removed when beta cells die off.

    We can slow PCa by targeting IGF & its over-expressed receptors.


    See my response to cesanon.

  • Hi martingugino

    I like to direct you to my enquiry to hysir. Please check inflammation and immunology on verywell.com/ immunology. You will be amazed by what you find.

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