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Biotech Medicine

Discovery of "Cancer-Proof" Rodent Cells 118

Posted by kdawson
from the don't-crowd-me dept.
anglico sends news of research out of the University of Rochester that has identified a gene that "cancer-proofs" cells in rodents. "Despite a 30-year lifespan that gives ample time for cells to grow cancerous, a small rodent species called a naked mole rat has never been found with tumors of any kind — and now biologists at the University of Rochester think they know why. The findings, presented in the Proceedings of the National Academy of Sciences, show that the mole rat's cells express a gene called p16 that makes the cells 'claustrophobic,' stopping the cells' proliferation when too many of them crowd together, cutting off runaway growth before it can start. The effect of p16 is so pronounced that when researchers mutated the cells to induce a tumor, the cells' growth barely changed, whereas regular mouse cells became fully cancerous."
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Discovery of "Cancer-Proof" Rodent Cells

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  • by fuzzyfuzzyfungus (1223518) on Tuesday October 27, 2009 @09:57PM (#29892373) Journal
    Not only are they cold-blooded and eusocial, they are substantially immune [livescience.com] to certain types of pain. Plus, when their burrow is invaded by a snake, they will deliberately sacrifice peripheral members of the colony to protect the core.

    We are just lucky that they eat only tubers, and look more or less like vienna sausages with legs, or they would be a shoe-in for title of "socialist supervermin public enemy number 1".
  • by wizardforce (1005805) on Tuesday October 27, 2009 @10:17PM (#29892495) Journal

    The short answer is no. p16 would help stop a virus from causing cancer but it would not prevent the virus from infecting the cell. If you're curious about some of the research being done on the phenomena of viruses causing cancer then I'll direct your attention here [colostate.edu]. The HTLV-1 provirus hijacks p300 and CREB and uses them to reproduce its self. p300 is a transcriptional co-activator which basically means that it greatly increases the rate of transcription of a gene. p16 wouldn't stop the infection of the cell nor would it stop the virus from hijacking these cellular proteins. However, it would help keep cell division relatively under control.

  • Naked Mole Rats (Score:5, Informative)

    by kryptKnight (698857) on Tuesday October 27, 2009 @10:17PM (#29892499)

    For those of you who aren't familiar with them, naked mole rats are pretty weird in a bunch of other ways

    They lack the neurotransmitter that lets them feel pain, which is evolutionarily unique as far as I know. Their respiratory systems are adapted to handle the high concentrations of CO2 that build up in their burrows. Their metabolic rate is 2/3 of other similarly sized rodents, and they can slow it even further in times of need.

    Their behavior is even weirder. The colonies (200-300 in population) are organized eusocialy, ie in the same manner as a bee or ant colony. There in one queen, with a harem of 3-4 males that produce all the offspring for the entire colony. Like ants, naked mole rats form separate castes for diggers, soldiers, etc. Oh, and to top it all off their front teeth are on the outside of their mouths to help them dig.

  • by interkin3tic (1469267) on Tuesday October 27, 2009 @10:38PM (#29892639)

    Given that the popular literature is telling us that many cancers are caused by virii, what is the resistance to virus infection by these cells relative to the mouse cells?

    Good question!

    Most of the viruses strongly associated with cancer work by specifically inactivating proteins which safeguard against cancer, or they produce tons of a protein or several proteins that urges the cell towards mad replication. A virus infecting a cell often has a vested interest in seeing that one cell produce as much as possible to produce more virus. (If computers could reproduce themselves, undoubtedly some botnets would have their infected computers reproduce for much the same reason.) A major safeguard against cancer though is limiting cell division in most cells, so cells which are urged to divide without limits by a virus lack that major safeguard against cancer.

    In the event that a mole rat got infected with a virus that caused cancer in that manner, it would depend on what method the virus took to make the cell divide out of control. There might well be mole rat viruses which specifically inhibit p16. If one were to take a carcinogenic virus and make it infect mole rat cells, it seems p16 might prevent the viruses from causing cancer: From the actual PNAS article abstract: [google.com]

    we show that a combination of activated Ras and SV40 LT fails to induce robust anchorage-independent growth in naked mole-rat cells, while it readily transforms mouse fibroblasts.

    SV40 and I believe Ras (or maybe not) are viral proteins that cause cells to proliferate without limits ( ~ cancer), they don't have that effect in mole-rat cells.

    Human cells are actually somewhat claustrophobic even without p16. Culture human fibroblasts (as the authors did) and the cells will happily reproduce, but only until they coat the media and are touching other cells on all sides. Normal human fibroblasts don't pile up on top of each other. They do when they have activated Ras or SV40 LT though. Mole rat cells don't. Also mole rat cells cultured tend to be more spread out than cultured human cells. The authors show some more important molecular details.

    What would have been truly amazing would be if they had caused human cells to express p16 as mole rat cells do, and then demonstrated that human cells then are able to resist piling up in the presence of activated Ras or SV40 LT. I don't see it in the paper, so I'd suspect they tried doing that and it didn't work, and/or they had to do some more tinkering to get p16 to work in human cells and this will be even bigger news when they get it.

    I am not a virologist or cancer biologist, so please, all you mean virologists and cancer biologists out there, go easy on me!

  • by wizardforce (1005805) on Tuesday October 27, 2009 @10:39PM (#29892645) Journal

    If p16 functions the same way in humans as it does in mice does this open a potential alternative to telomere shortening and thus a pathway to the elimination of aging?

    No. As is the case with these moles, the indefinite extension of telomeres does not eliminate aging. Cell division requires that the genome be replicated and that requires a small segment of DNA be snipped off the ends of chromosomes. The telomeres act as a piece of code for this purpose that once sacrificed causes no real harm to the organism. The telomeres are repeats of the sequence TTAGGG in humans which forms hydrogen bonds with its self forming a quadruple helix acting as a cap for the ends of chromosomes. Once the telomeres are eliminated, the ends of chromosomes are treated as double strand breaks by genetic repair machinery which more often than not, results in apoptosis, chromosome joining and ultimately cancer in some cases. Much of aging has to do with genetic damage and incorrect methylation of base pairs in genes. Telomerase (the enzyme that extends telomeres) would not stop that kind of aging process.

  • by Anonymous Coward on Tuesday October 27, 2009 @10:52PM (#29892739)

    one of those symptoms being death

  • by Trebawa (1461025) <trbawa AT aol DOT com> on Tuesday October 27, 2009 @10:56PM (#29892777)
    The thing is, that's one of the things that defines cancer, so this is an important step towards defeating it. Cancer isn't one disease; it's pretty much any mutation (or, more commonly, series of mutations) that make a cell or group of cells override the checks that the body usually puts on division. Cancer cells don't exhibit density-dependent inhibition like normal cells; it sounds like this p16 gene can help enforce this despite mutations in what are normally oncogenes.
  • by Stiletto (12066) on Tuesday October 27, 2009 @10:57PM (#29892783)

    Pet Peeve: What the hell is a "virii"? Don't you mean "viruses"? [archive.org]

    Jeez...

  • by wizardforce (1005805) on Tuesday October 27, 2009 @11:27PM (#29892967) Journal

    Cancer cells are indeed immortalized and can live on their own practically indefinitely. However, they also have numerous mutations that change their cellular physiology significantly. Immortalization allows for indefinite cell reproductive life but it does not in of its self grant that life.

  • Re:Wrong. (Score:5, Informative)

    by wizardforce (1005805) on Wednesday October 28, 2009 @12:02AM (#29893127) Journal

    technically naked mole rats are considered "operational poikilotherms." Their body temperature varies drastically depending on the temperature of their environment due to their very limited ability to control their own body temperature.

    They may not perceive certain types of pain, but that is not "immunity".

    I'm guessing you failed high school biology?

    The definition of "immunity" in the English language is not restricted to an immunity to disease.

  • by wizardforce (1005805) on Wednesday October 28, 2009 @01:30AM (#29893469) Journal

    That telomeric shortening does not occur in many different species. They age just like every other species does. But that is all beside the point. You can't just shut off aging just by fixing the telomeres; aging is a much more complicated problem than that.

  • by wizardforce (1005805) on Wednesday October 28, 2009 @01:36AM (#29893501) Journal

    every time a cell divides, there's a chance that the DNA won't get copied quite correctly. The error rate is around 1 in 10^9 for humans and varies from species to species. The more times the cell divides, the more errors accumulate. Immortalization doesn't just switch off the damage as it seems that you are thinking that it would. It just means that the number of times the cell can divide isn't limited by telomere length any more.

  • by Anonymous Coward on Wednesday October 28, 2009 @01:56AM (#29893601)

    or they would be a shoe-in

    The phrase is "shoo-in", not "shoe-in".

  • Missing the point: (Score:5, Informative)

    by Hartree (191324) on Wednesday October 28, 2009 @05:57AM (#29894573)

    I think there's some misunderstanding of what the PNAS article says.

    P16 is a known tumor supressor gene. It's also in humans. Think of it (and P27, another tumor supressor gene, as well) as sprinkler systems that get set off in response to the fire of excess cell proliferation.

    What they found was that in the mole rats, the cells were much more sensitive to crowding than human cells were. Apparently, there is a second crowding detecting system in the mole rats that is more sensitive. They also have the less sensitive crowding detecting system that humans have.

    Further, they found that this early crowding signal "set off" (caused expression of)the P16 supressor. The less sensitive crowding detection system that both humans and mole rats have instead "sets off" the P27 tumor supressor gene.

    Just having the P16 gene isn't the whole story, humans have it too. It's the entire chain of signals that "sounds the alarm" from mild crowding of the cell and proceeds to the expression of P16. Knowing that it's P16 that gets expressed gives a starting point to figure out the rest of the system.

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