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Discovery of "Cancer-Proof" Rodent Cells
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."
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?
Do not mock my vision of impractical footwear
before our resident EMH comes equipped with a p16 loaded hypospray?
I'm not worried. I always use poison or traps anyway. You see, its just to difficult to reliably give them cancer.
Judging by the story, and in the context of my almost complete lack of formal training in cell biology, it sounds like the cells might not be resistant to cancer-causing virii, but rather it just means the infected cells can't multiply past a certain point. Sort of like carrying a disease but not showing any symptoms.
Not only are they cold-blooded and eusocial, they are substantially immune 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".
You're not going to get a Nobel for something that only works on lawyers.
Resistant, nay, impervious to cancer? So that's the sitch she was always talking about!
Most men are not thought unwise until they speak.
I for one say welcome to our cancer immune naked mole rat overlords.
When It Counts.
All organisms have these kinds of tumor suppressor genes whether they act to inhibit cell proliferation or promote cell death, in fact most cancers have to have mutations that inhibit these suppressor genes as well as mutations which enhance genes that promote cell growth and proliferation. What would be more interesting than simply identifying the suppressor gene(s) believed to be the cause of the absence of naked mole rat cancers would be in identifying the mechanisms that have protected that(those) gene(s). I wonder if the researchers in question also considered alternate explanations for the absence of cancers in naked mole rats- its very possible that their subterranean environment simply doesn't contain as many mutagens as we are exposed to and as such having a naked mole rat with a mutated (inhibited) tumor suppressor AND a mutated (enhanced) tumor promoter is such a rarity that we simply haven't been able to find one.
I'll be happier dying at age 50 of cancer than looking like a naked mole rat!
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. 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.
Sigs are too short to say anything truly profound so read the above post instead.
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.
Facts do not cease to exist because they are ignored. -Aldous Huxley
Rodents of Unusual Resistances? I don't think they exist.
oh yah? i saw that early today or yesturday. but don't hate on me for that plz nice though... interesting... i wonder how this relates to SENS?????
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They already look the way that they do *and* they're called naked mole rats.
On top of that they should get cancer?
I see even classic Slashdot is now pretty much unusable on dial up anymore.
My understanding is that one of the primary causes of aging in humans is that a protein that extends telomeres after cell division is turned off in most cells. Additionally as I understood it the only purpose of turning production of this protein off is to prevent cancer.
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?
OK... so they're naked already. How do I get me a date with one of these rats? Do I need duct tape?
I want the fruits of my loins to be cancer free.
Just doing my bit for humanity
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:
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!
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.
Sigs are too short to say anything truly profound so read the above post instead.
... and I realize now you were asking about infection, not cancer, so uh...
one of those symptoms being death
With cancers caused by viral infections, it seems that the proliferation of cell division that is cancer is a secondary effect. HTLV-1 provirus as an example causes cancer in only about 3% of infected individuals. It hijacks the normal functions of p300 and creb using its own TAX protein encoded in the virus' genome to massively upregulate the production of its own proteins. Cell cycle regulation is often disrupted as a result of this meddling by the virus.
Sigs are too short to say anything truly profound so read the above post instead.
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.
Pet Peeve: What the hell is a "virii"? Don't you mean "viruses"?
Jeez...
Now you know how I feel when there's an article about API's, Ubuntu, or codecs.
Human cells have and express p16-INK4A normally - it's part of the CDKN2A gene locus. It is a cell cycle control gene whose main function is to put the brakes on replication. p16 is expressed in human cells and is often mutated or outright deleted in many human cancers of all cell types.
COSMIC (new window)
The difference described in naked mole rats is that their cells induce p16 expression after minimal contact with neighboring cells while human and rat cells need more prodding to turn on cell cycle control genes.
This is a cool finding, but does not have a direct application in human cancers anytime soon. It's very hard to turn on a gene that has been mutated or deleted in cancer cells. You have to do it in practically every cell, otherwise, they grow back. Even then it may be too late. Loss of contact inhibition may be necessary in early oncogenesis, but restoration of p16 expression in a cancer cell that already has multiple genetic mutations, may not do much at that point. So, it's an interesting finding and I hope it leads to a better understanding of cancer and cancer prevention. But honestly, we have cool findings like this once a week. It just requires the right spin to sell it to the media - like calling something a "cancer-proof" gene - and it finds its way here.
The tobacco companies just gained tens billions of potential customers.
I am an undergraduate at UC Berkeley and am currently taking a class on cancer, especially the genetic basis for its development. One of the professors is Steve Martin, a famous cancer researcher. Even if I wasn't in this class, I would know that p16 is a well-known gene. They definitely did not discover it in this study. This article is very misleading. Humans definitely have p16, is it vital to the normal cell cycle. It is also frequently mutated in melanomas, one of the most vicious cancers. It is most likely that this group has found that naked mole rat cells use p16 in a unique way as it relates to certain types of cancer transformation pathways. Bear in mind that this sounds like this was a completely in vitro study, and so there is no proof this this gene behaves this way in wild mole rats.
All that being said, this could still turn out to be a big discovery. If they can identify the molecular mechanism behind the improved cancer suppression, it could lead to novel treatments.
Beware the Jubjub bird, and shun the frumious Bandersnatch.
This is not strictly true. There are cell lines that are so-called 'immortalized', and have been dividing continuously for many years with no signs of slowing down. They typically have very high expression of telomerase and other protective factors. Cancer can be thought of as an immortalized cell line in a living body.
Beware the Jubjub bird, and shun the frumious Bandersnatch.
Chemotherapy drugs seem to rely on this already. The problem is that we need some cells in our body to proliferate. For example in the bone marrow, the digestive system and the immune system. My wife's father died from a toxic reaction to chemotherapy drugs when the drug killed his bone marrow.
I would be more interested if this technique could be more selective in the tissues it impacts, but then you still have to treat cancer in normally fast growing tissues.
http://michaelsmith.id.au
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.
Sigs are too short to say anything truly profound so read the above post instead.
Or no longer present articles on perl.com.
Please don't spread your misinformation to others.
Mammals are by definition, warm blooded. These animals do have a difficult time controlling their body temp, but that does not make them cold blooded.
They also are not 'immune' to pain. Immunity is by definition resistance to infection from other organisms such as bacteria and viruses. Pain is not another organism, its a sensation the brain generates based on the signals sent by nerve endings throughout different parts of the body. They may not perceive certain types of pain, but that is not "immunity".
I'm guessing you failed high school biology?
They aren't a particularly impressive vermin, their inability to control their own temp puts severe constraints on where they can live and what they can do. The would, for instance, not survive in most of the united states for most of the year without remaining a fair distance underground, in which case they are of little threat to much of anything other than some plants with deep roots.
Your potatoes are still safe, since they would freeze to death in the winters where most potatoes are grown, and most people keep their homes below an acceptable temp for them to reside in doors.
Theres a reason they live in the desert.
Persistent Volume manager for Kubernetes - https://github.com/dwimsey/openshift-pvmanager
telomeres can be thought of as one part of the aging process. if the person you responded to had talked about DNA methylation or mutations, you could have responded by saying "well what about telomeres!" my point is that its involved, and from what I have been taught they play quite a large role in aging.
Beware the Jubjub bird, and shun the frumious Bandersnatch.
Cool.
However, according to the article, they found the same anticancer mechanism in other small, long-lived rodents like common gray squirrels, so this is probably not related to any of those other abilities.
No wonder considering they may be relatives to the pan-dimensional, hyper-intelligent race of beings.
In theory there is no difference between theory and practice. In practice there is. - Yogi Berra
They serve as a longevity boundry. That is why they are important. However, their continued presence does not play as large a role in aging as was once believed.
Sigs are too short to say anything truly profound so read the above post instead.
that's a little silly to say. are you suggesting that telomeres evolved to place an upper limit on an organism's lifespan? I doubt you believe that.
telomerase is expressed at very low levels in adult somatic cells -> telomeres shorten, eventually get lost -> genes get lost. in what way is this not a large part of aging?
Beware the Jubjub bird, and shun the frumious Bandersnatch.
So, the secret to cancer prevention is to get naked?
Excuse me, I have a new pickup line I need to try out...
Captcha: Polite
1. Set up a Gene bank with intact chromosomes from when your in your 20-30's.
2. Replace old you genes with young you genes?
3. Profit! (Immortality!)
"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."
So the way in which p16 is believed to protect cells from cancer does not conflict with turning on telomerase and turning on telomerase would prevent this kind of damage causing at least some impact on aging and cell damage.
"Much of aging has to do with genetic damage"
Wouldn't immortalizing healthy undamaged cells counteract this to some extent?
If nothing else it would seem as if this may at least be part of the puzzle along with increased antioxidants, sunscreen, and viagra.
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.
Sigs are too short to say anything truly profound so read the above post instead.
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.
Sigs are too short to say anything truly profound so read the above post instead.
I found it a rather profound show and watched the DVD several times in a row. Note that the 2005 BBC version (on YouTube) is quite inferior to the 2006 WGBH/Nova one I managed to find on de.sevenload.com. Here are the 6 parts, TinyURL'd: 1 2 3 4 5 6.
I come here for the love
really? how do you explain how those species overcome the end replication problem? we agree that aging is more complex than just telomeres... nobody thinks that. perhaps in the mainstream media.
i never said that telomeres were the answer to aging. but i did say that highly active telomerase is a characteristic trait among immortal cell lines. and that they are deeply involved in the aging process, especially in humans (which is the species in question). yes, many (not all) of those lines are messed up in one way or another. the point stands though: if there is a possibility of extending human lifespans through biotechnology, you can be sure that telomeres will be involved. i mean, just think of cancer. telomeres and telomerase are a key component of how cancer manages to sustain such explosive growth. if we had a good telomerase RT inhibitor, it would help greatly against cancer. once we do, average human age will necessarily increase, ergo biochemical control of telomeres is intimately related to aging.
Beware the Jubjub bird, and shun the frumious Bandersnatch.
cancer is not caused by virii but by mistakes within the cells.
Limiting division by telomere length kills off healthy and undamaged cells preventing them from dividing. Removing this "feature" while introducing a replacement mechanism to protect from cancer would leave only damaged cells unable to reproduce.
All else being equal that should increase the ratio of undamaged cells to damaged cells.
I really don't see how anyone could deny that would be a good thing.
given a proper genetic repair mechanism, improved and redundant cell cycle regulator genes and telomerase then sure, you could increase human lifespan. These cells only need to replicate themselves to replace damaged cells so hardening cells against genetic damage in of its self significantly reduces the need for the cell divisions that degrade the telomeres in the first place.
Sigs are too short to say anything truly profound so read the above post instead.
http://nationalzoo.si.edu/Animals/SmallMammals/default.cfm?cam=NMR
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.
If you're constantly exposed to cancerous substances by sadistic humans in white lab coats, your decendants would obviously develop a resistance to cancer!
No, he means "virus".
I fail to see how a virus could cause cancer because the whole point of a virus is to reproduce. To do this it infects a cell, reproduces inside the cell until the cell dies and basically explodes, scattering the virus back into the wild where it infects more cells. Cancer does not suffer from cell death or explosion, in fact it is pretty much the opposite. If cells were exploding then the immune system would notice something going on, which in the case of cancer, it doesn't. So how does the virus spread if it's stuck inside a steadily growing cell ?
Now that this has made the news I expect that 'Mole Rat Extract' will soon be apearing in spam as the next curall for cancer. Of coruse 'Big Pharma' will be keeping it secret but you can buy it from our site for only $699.00 per dose.
Undetectable Steganography? Yep, there's an app fo
The plural form of virus is "viri" not virii.
Waitaminute-- I know this shouldn't be a revelation, but they can easily and reliably induce tumors? I know that this is just a function of killing cells off repeatedly in an area, or applying some radiation therapy, but does this scare anyone else? I know we should be focusing on the notion of a cure here, but I can't help but be alarmed that it is de rigueur to be able to induce tumors at a whim, for experimental purposes or not.
It's very hard to turn on a gene that has been mutated or deleted in cancer cells. You have to do it in practically every cell, otherwise, they grow back.
Right, which is why it'd have to be a built-in, like with the naked mole rats, rather than a plug-in. There are benefits to static linking!
-l
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i cant help but think its marred by the overtone that most americans could engage in some very simple lifestyle changes to avoid cancer.
quit eating so much red meat, cut back on a diet of food enriched with various synthetic hormones, and eat more fruits and veggies. 2-4 cups of green or white tea a day would be an excellent start as well. Go for a run. But no, any suggestion to the contrary of a full rack of babybacks and a milkshake followed up with a slice of cheesecake and a cigarette afterwards is touted as "taking away my freedom!"
Good people go to bed earlier.
Still no cure for... oh, wait.
I void warranties.
So that's why they were able to survive the bombs dropped by those red commie bastards and are still able to chew right through my power armor....
How did they get so big though?
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what happens if the p16 gene mutates?
or if something around the gene mutates (changing the geometry of the dna near it and making it inaccessible)and prevent it from expressing itself?
just guessing....
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.
I was just talking to a woman getting her PhD in oncology the other day at a wedding (boy did THAT conversation make everyone else's eyes glaze over) and she said that their research was into how DNA gets acylated rather than methylated, which seems to be strongly correlated with development of cancer. I'd never heard of such a thing, and thought it was really interesting.
As a side-note, I got my degree in biochem from CSU and took classes from a lot of the people referenced in that link you provided. I dunno what Jennifer Nyborg is like now, but back when I was taking classes, the whole class had a crush on her.
Nostalgia's not what it used to be.
Does "naked" imply it is hairless? or does it just have a different belief system than it's clothed cousins?
Seriously, does the gene also prevent the "runaway growth" of cells that produce hair?
If I were to get some gene therapy for p16, will my hair stop growing everywhere?
What else? my finger nails?
Maybe my ability to condition my body to environmental changes will be drastically slowed as well.
I love this cutting edge research stuff, but I would hate to be the one "staking claim" to any discovery because it seems they can't explain JACK SHIT. If they could come up with a unified theory for biology, they could predict this stuff exists or could exist.
Please - spend more time understanding what the JUNK in my DNA is really about!
Like the guy who "discovered" the mem-resistor through inductive proof, that was awesome.
More correctly, the "cancer" would still happen but there would be an extra regulatory mechanism so that it wouldn't be nearly as prolific. At it's best, it would be almost like not having cancer. With luck, the slower proliferation would give the immune system a chance to clean up the mess. If not, it would be a lot easier for an oncologist to clean up the mess.
If my doctor said virii, I'd be concerned. If my IT director said viruses, I'd be concerned.
Hi, Mr. Coward. I'd like you to meet Mr. HPV.
Was this not mentioned in New Scientist recently - from memory Humans have one hurdle for Cancer to overcome while the naked mole rat has two hurdles making it so much harder to start the cancer process.
Wow! After we all die of cancer, the rats can take over. Oh wait, they're in Washington and have already done so!! That means the cancer fighting drugs for us humans will be too expensive....
Amazing!
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