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p53 study conducted by scientists at the U.S. Department of Energy's (DOE) -this explains a bit about p53's role in cancer.

california_artist
Posts: 850
Joined: Jan 2009

First Analysis of Tumor-Suppressor Interactions With Whole Genome in Normal Human Cells Reveals Key Differences With Cancer Cells
ScienceDaily (Nov. 30, 2011) — Scientists investigating the interactions, or binding patterns, of a major tumor-suppressor protein known as p53 with the entire genome in normal human cells have turned up key differences from those observed in cancer cells. The distinct binding patterns reflect differences in the chromatin (the way DNA is packed with proteins), which may be important for understanding the function of the tumor suppressor protein in cancer cells

The study was conducted by scientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory and collaborators at Cold Spring Harbor Laboratory, and is published in the December 15 issue of the journal Cell Cycle.
"No other study has shown such a dramatic difference in a tumor suppressor protein binding to DNA between normal and cancer-derived cells," said Brookhaven biologist Krassimira Botcheva, lead author on the paper. "This research makes it clear that it is essential to study p53 functions in both types of cells in the context of chromatin to gain a correct understanding of how p53 tumor suppression is affected by global epigenetic changes -- modifications to DNA or chromatin -- associated with cancer development."
Because of its key role in tumor suppression, p53 is the most studied human protein. It modulates a cell's response to a variety of stresses (nutrient starvation, oxygen level changes, DNA damage caused by chemicals or radiation) by binding to DNA and regulating the expression of an extensive network of genes. Depending on the level of DNA damage, it can activate DNA repair, stop the cells from multiplying, or cause them to self-destruct -- all of which can potentially prevent or stop tumor development. Malfunctioning p53 is a hallmark of human cancers.
Most early studies of p53 binding explored its interactions with isolated individual genes, and all whole-genome studies to date have been conducted in cancer-derived cells. This is the first study to present a high-resolution genome-wide p53-binding map for normal human cells, and to correlate those findings with the "epigenetic landscape" of the genome.
"We analyzed the p53 binding in the context of the human epigenome, by correlating the p53 binding profile we obtained in normal human cells with a published high-resolution map of DNA methylation -- a type of chemical modification that is one of the most important epigenetic modifications to DNA -- that had been generated for the same cells," Botcheva said.

Key findings
In the normal human cells, the scientists found p53 binding sites located in close proximity to genes and particularly at the sites in the genome, known as transcriptions start sites, which represent "start" signals for transcribing the genes. Though this association of binding sites with genes and transcription start sites was previously observed in studies of functional, individually analyzed binding sites, it was not seen in high-throughput whole-genome studies of cancer-derived cell lines. In those earlier studies, the identified p53 binding sites were found not close to genes, and not close to the sites in the human genome where transcription starts.
Additionally, nearly half of the newly identified p53 binding sites in the normal cells (in contrast to about five percent of the sites reported in cancer cells) reside in so-called CpG islands. These are short DNA sequences with unusually high numbers of cytosine and guanine bases (the C and G of the four-letter genetic code alphabet, consisting of A, T, C, and G). CpG islands tend to be hypo- (or under-) methylated relative to the heavily methylated mammalian genome.
"This association of binding sites with CpG islands in the normal cells is what prompted us to investigate a possible genome-wide correlation between the identified sites and the CpG methylation status," Botcheva said.
The scientists found that p53 binding sites were enriched at hypomethylated regions of the human genome, both in and outside CpG islands.
"This is an important finding because, during cancer development, many CpG islands are subjected to extensive methylation while the bulk of the genomic DNA becomes hypomethylated," Botcheva said. "These major epigenetic changes may contribute to the differences observed in the p53-binding-sites' distribution in normal and cancer cells."
The scientists say this study clearly illustrates that the genomic landscape -- the DNA modifications and the associated chromatin changes -- have a significant effect on p53 binding. Furthermore, it greatly extends the list of experimentally defined p53 binding sites and provides a general framework for investigating the interplay between transcription factor binding, tumor suppression, and epigenetic changes associated with cancer development.
This research, which was funded by the DOE Office of Science, lays groundwork for further advancing the detailed understanding of radiation effects, including low-dose radiation effects, on the human genome.
The research team also includes John Dunn and Carl Anderson of Brookhaven Lab, and Richard McCombie of Cold Spring Harbor Laboratory, where the high-throughput Illumina sequencing was done.
Methodology The p53 binding sites were identified by a method called ChIP-seq: for chromatin immunoprecipitation (ChIP), which produces a library of DNA fragments bound by a protein of interest using immunochemistry tools, followed by massively parallel DNA sequencing (seq) for determining simultaneously millions of sequences (the order of the nucleotide bases A, T, C and G in DNA) for these fragments.
"The experiment is challenging, the data require independent experimental validation and extensive bioinformatics analysis, but it is indispensable for high-throughput genomic analyses," Botcheva said. Establishing such capability at BNL is directly related to the efforts for development of profiling technologies for evaluating the role of epigenetic modifications in modulating low-dose ionizing radiation responses and also applicable for plant epigenetic studies.
The analysis required custom-designed software developed by Brookhaven bioinformatics specialist Sean McCorkle.
"Mapping the locations of nearly 20 million sequences in the 3-billion-base human genome, identifying binding sites, and performing comparative analysis with other data sets required new programming approaches as well as parallel processing on many CPUs," McCorkle said. "The sheer volume of this data required extensive computing, a situation expected to become increasingly commonplace in biology. While this work was a sequence data-processing milestone for Brookhaven, we expect data volumes only to increase in the future, and the computing challenges to continue."
Where proteins bind: Scientists used the "ChIP-seq" technique to identify where p53, an important tumor suppressor protein, binds across the entire genome in normal human cells. After cross-linking the protein to DNA, they split open the cells and used a specific antibody to identify and isolate the chromatin fragments containing the bound protein. Then they purified those DNA fragments and used high-throughput sequencing techniques and computational analysis to map millions of sequenced fragments to the genome. The main finding -- that p53 has a different binding pattern in normal human cells compared with that previously observed in cancer cells -- may have implications for understanding the suppressor protein's function. (Credit: Image courtesy of DOE/Brookhaven National Laboratory)

I Will Survive
Posts: 27
Joined: Aug 2011

Did we really need THREE new threads about p-53 AND yet another thread about turmeric and taxol? These topics have been discussed and re-discussed, and ALL has been said, ad nauseum***, many times before. Ye gods. Wake me when something new is posted.

***Ad nauseam

Ad nauseam is a Latin term used to describe a discussion which has been continuing "to [the point of] nausea". For example, the sentence, "This topic has been discussed ad nauseam", signifies that the topic in question has been discussed extensively, and that those involved in the discussion have grown tired of it.

Hannah

RoseyR
Posts: 464
Joined: Feb 2011

Thanks, Claudia,

Particularly for the sake of newcomers to this site--who hardly have time to scroll back to find important subjects addressed months ago--your new messages give credibliity to the claim that cancer-controlling genes can be altered, and even repaired, via diet and other environmental mechanisms.

This one explains for the first time on the board the intricate dynamics by which the P53 gene works.

If I feel I know all there is to know about the subject of a new post, I can easily scroll away from it. I am never bothered by a subject that--however often it has been introduced--offers a new angle on it, or a new source of authority on it, or that could be vital to newcomers, potentially helping to prolong their lives.

I would, for example, like to see MORE about the impact of Vitamin D, alpha lipoic acid, and melatonin on cancer patients. The role of whole grains in our diet is an" old" subject, but one hardly resolved; controversy grows about whether they raise our blood sugar levels too quickly.

Even curcumin is hardly a "closed book" as some members question supplements of ANY kind whereas newcomers might want to investigate its possible action against inflammation.

Appreciatively,
Rosey

california_artist
Posts: 850
Joined: Jan 2009

The three threads seemed to complement one another, and might open avenues of thought, especially for those newly diagnosed.

As you are very interested in the why's and wherefore's of cancer's origin and progression, I thought you might find Dr. John Boik's books of use.

I had emailed him at Stanford regarding our situation, suggesting that women on the board would be willing to inform him of things we had done, after discussing it with the group at that time.
He explained he was a statistician, and so more of a numbers kinda guy. His books have gotten rave reviews from the scientific community.

His closing reminded me of how I used to close my posts. From Dr. John Boik:

Hi Claudia:
I'm happy that my book was of use to you. Did you know it is available for free download from www.ompress.com?I'm not working on any new books....maybe in a few years. For now I have my hands full just trying to get some lab work accomplished.

I agree, love, hope, success, health and joy to us all!

John

I don't know if it is still available from the url he suggests, and at the time it had been $400 on amazon.

I still wish love, hope, success, health and joy to us all!

Claudia

Gracegoi's picture
Gracegoi
Posts: 59
Joined: Aug 2011

I know others have read his Book. I have not yet . I'm not very good with reading, suffering from slight dyslexia and ADHD so I apperciate these summaries Claudia.

I agree with Rosey , newcombers like to see this either through Bumps of old posts or refreshers.

Keep on Scrolling. :-)

Grace

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jazzy1
Posts: 1387
Joined: Mar 2010

Repetition is good at least for one like myself with chemo brain. We're all so rushed and some things which are posted again, might even have more qualified updates, etc. I for one don't take in everything the first time when read, so repeating again helps.

Grace, yes newbies don't get a lot of this stuff, as most don't search for past postings, not knowing what we're posted in past. Refreshers are great!!

Keep 'em coming...if you don't like that it's repeated (makes one yawn), click off the topic and pull up one which is best for your happy reading. I don't read everything and if it's something of no interest, amazingly the buttons on my keyboard direct me to other places.

To each his own.....
Jan

Rewriter's picture
Rewriter
Posts: 494
Joined: Dec 2009

Thank you for all that you do to keep us informed about new studies, treatments, dietary approaches, and related information on how to deal with a cancer diagnosis. As important, thank you for updating each key topic whenever new information becomes available. This is critically important to me.

New board members are not going to scroll back looking for information on something they are not aware exists. I knew nothing about the P53 gene until you shared an article about its role in cancer. The same with the curcumin and turmeric studies--you posted that info first; and I'm gratified that the pertinent information gets repeated often. I'm lucky that you are so vigilant, and I am more grateful to you than I can say.

Keep the updates coming. Post critically important information often. As Jan indicated, our keyboard mouse is a nifty little creature capable of moving us away from a thread that holds no interest for us.

Jill

Kaleena's picture
Kaleena
Posts: 1126
Joined: Nov 2009

All I can tell you ladies is this: Since I started on this site, I have gained so much information. I had my six month check up on December 12th and was advised that I had lost 10% of my body weight from my June appointmnet. None of my previous doctors or other facility had ever advised me or directed me into a way of eating for 1) having a hysterectomy; and 2) having chemo.

I had originally gained 30 pounds while on chemo back in 2005/2006 and because of the hysterectomy more weight kept creeping on. When I asked the doctor about the weight gain he told me "americans eat too much". Ahhhh. How about asking me what I ate? etc. etc.

Anyway, from all of your inputs I gathered information that has helped not only me but my family. I previously lost 7 pounds in the past year or so but most recently lost 25 pounds (in 6 months) from eating healthy food and making healthy choices. My husband has lost 75 pounds. I used some of the receipes we exchanged and other information (although at first I did have stomach problems from eating healthy!)

So I just want to thank you ladies for all of your input. I may not always comment or post about it, but I do take information that can apply to me.

Thank you!

Kathy

HellieC
Posts: 440
Joined: Nov 2010

Thanks for posting, Claudia. Any information is helpful and bringing forward that which may be "lurking at the back" really does help those new to the boards who may be searching for answers to their particular issues.
Like the other ladies said, we don't have to read or comment on everything on the board - it's quick and easy to move on and find something which interests us, or where we think we can contribute something useful.
Thank you!
Helen

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