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Tag Archives: p53

Friday Science Review: March 26, 2010

Why Did the Duck Kill the Chicken? Well… a scientific explanation is RIG-I.  Ducks are resistant to influenza viruses but may by asymptomatic carriers.  One of the reasons for ducks’ resistance is because ducks express the RIG-I protein that senses the presence of the viruses.  Chickens, however, do not appear to express RIG-I or a similar protein and have no method to detect the presence of viruses to illicit an immune response.  This could have implications to the poultry industry who do not want to see their entire farm wiped out by a viral outbreak and may want to start breeding transgenic chickens expressing RIG-I.  The discovery was led by Dr. Katharine Magor and her team at the University of Alberta and is published in the early edition of the Proceedings of the National Academy of Sciences.

Promoting Cancer Cell Growth: The YB-1 (Y-box binding protein-1) transcription factor is a known oncogene that is expressed in a significant percentage of breast cancers.  In this study, scientists demonstrated that YB-1 induces the expression of CD44 and CD49f, which are associated with cancer stem cells and used as stem cell markers.  Although they do not make a direct link to breast cancer stem cells, they suggest that it is this link that explains why YB-1 expressing cancers are resistant to drugs such as paclitaxel and are associated with disease recurrence and poor outcome.  The principal investigator of the study was Dr. Sandra Dunn at the University of British Columbia. Details of the study were reported in Cancer Research.

Knock, knock… Let Me In: A transporter protein that is selectively expressed in blood cells can be manipulated to facilitate the entry of cancer drugs into the cell.  This is extremely important for new treatment regimes against blood cancers such as AML and other leukemias.  Researchers found that the Human Carnitine Transporter encoded by the SLC22A16 gene acts as a gateway and can mediate the uptake of the polyamine class of drugs such as the anti-cancer agent Bleomycin.  Dr. Dindial Ramotar, Université de Montréal, first demonstrated this in yeast cells and now in human cells as reported in the Journal of Biological Chemistry.

Please, No More Radiation: A genetic mutation in the p53 gene in children with a rare type of brain cancer – choroid plexus carcinoma (CPC) – is a new marker indicating a poor response to radiation therapy.  It is unfortunate that this signals a more aggressive disease, however, this finding would relieve the patient of having to suffer through the difficulties of radiation.  The inherited p53 mutation is associated with a condition called Li-Fraumeni syndrome and is found in about 50% of CPC cases.  Without the mutation, CPC patients treated by radiation have a good chance of recovery.  The study, led by Dr. David Malkin at the Hospital for Sick Children, Toronto, is published in the advance online issue of the Journal of Clinical Oncology.

Mooooooooo: Scientists have finished sequencing the genome of two different types of cows – one beef and one dairy – using Life Technologies’ next generation SOLiD™ 3 System.  It cost $130K and took only seven months to complete.  In comparison, it cost $50M and four years, finishing in 2009, to sequence the first cow.  The genomic information is important to the industry for making breeding decisions and to identify genetic markers of specific desirable traits.  So that T-bone steak waiting for you to grill up this summer will be even juicier and tastier.  The Bovine Genomics Program at the University of Alberta led by Dr. Stephen Moore performed the sequencing study.

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Friday Science Review: November 6, 2009

Just two stories this week – a cancer pathway and innovative dipsticks…

New Relationship between Tumour Suppressor Genes: Knocking out genes in mice believed to play a tumour inhibiting role would intuitively result in rapid cancer development.  However, it was a surprise to McGill researchers that mice lacking the tumour suppressors 4E-BP1 and 4E-BP2 were refractory to cancer growth.  When they deleted another well known tumour suppressor, p53, then they observed enhanced tumour growth more aggressive than knocking out p53 alone.  These results demonstrate for the first time a cooperative effect between 4E-BPs and p53 and highlight the advantages of indentifying individual molecular profiles to predict responsiveness to therapeutic strategies.  Dr. Nahum Sonenberg, who led the research team at McGill University remarks “this is another fine example how basic research, which intends to provide answers to fundamental questions about molecular mechanisms of cell proliferation, leads to unexpected findings that advance our ability to understand and cure human disease.”  The study appears in this week’s issue of Cancer Cell.

Bioactive Paper Sensors: A simple and rapid method to detect pesticides or toxins in food using innovative test strips was recently developed at McMaster University.  These “dipsticks” can sense the presence of small amounts of pesticides in food and within five minutes, a colour change indicates the level of the contaminant.  Future applications of this technology, with a few tweaks,  include detecting for the presence of food borne bacteria such as E.coli, Listeria, or Salmonella.  The practicality, ease of use without the need for large equipment, and the ability to get almost immediate results are huge advantages of the dipsticks to provide rapid screening and could play a role in curbing future outbreaks.  Dr. John Brennan’s team describes their research in the latest issue of Analytical Chemistry.

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Friday Science Review: August 28, 2009

A Montreal flavour this week…

Critical link between EGFR and Src oncogenes: On the heels of last week’s Friday Science Review post on Stat3 in breast cancer, Dr. William Muller’s research team at McGill University has published another significant find linking well known oncogenes, Src and EGFR/ErbB2.  Among their results, they demonstrated how Src can interact with some mutant EGFR receptors (identified in lung cancers) but not with wild type EGFR.  When a Src inhibitor was applied to cells expressing mutant EGFR, it attenuated the cancer-inducing potential of these EGFR mutants.  This suggests that Src is an important enzyme in the EGFR mutant signaling pathway and may present an alternate pathway to combat cancer cell resistance to EGFR inhibitors.

Details of this study are described in this week’s Molecular and Cellular Biology.

MET oncogene in breast cancer: Next door to the Muller Lab at the new Goodman Cancer Centre in Montreal is Dr. Morag Park and her research team who recently generated a mouse model to mimic and study the Met oncogene in breast cancer.  The results were a complex cancer phenotype where gene expression and histological profiles demonstrated similarities to aggressive human breast cancers expressing Met.  Whereas prior to their study, Met was only correlated with poor outcome in breast cancer patients, this mouse model provides the specific link and identifies clinical cases where anti-Met therapy may be beneficial.

You can read more about it here in Proceedings of the National Academy of Sciences.

Key proteins in Natural Killer Cells: Also this week, Dr. André Veillette’s lab at the Institut de recherches cliniques de Montréal (IRCM) generated new insight into how Natural Killer Cells combat cancers of the blood, such as leukemias and lymphomas, or virus-infected blood cells.  As part of our immune system, the defense function of Natural Killer Cells requires three small proteins named SAP, EAT-2 and ERT that are unique to immune cells.  The proteins relay information from the cell surface SLAM family receptors to direct immune activities.  These data may eventually lead to pharmacological methods to increase the activity of Natural Killer Cells in destroying blood cancer cells or virus-infected cells.

Veillette’s lab generated knock-out mice missing all three proteins, which led to their findings, which are published in the latest edition of Nature Immunology.

p53 is regulated by JNK: p53 is a tumor suppressor protein that plays an important role in regulating cell growth and survival.  Its critical functions in the cell require p53 to be highly regulated through multiple layers of control, both to turn on and to turn off the protein’s activities.  One such method recently described in Proceedings of the National Academy of Sciences is through phosphorylation by the enzyme JNK.  This phosphorylation protects p53 from being targeted for destruction, thereby allowing p53 complexes to form and continue with their gene activating activities.

This research project was a collaboration between the Burnam Institute in San Diego and Dr. Katherine Borden’s team at the Université de Montréal.

Jurassic Park (for real?): Can you convert a chicken embryo to develop into a dinosaur?  No, this is not the makings of a movie but the idea of paleontologist Hans Larsson of McGill University who is proposing to try to make it work.  The theory is that by manipulating or swapping certain “switch” genes during the chicken embryo’s development, he can reproduce some features of a dinosaur.  He does not actually intend to hatch live prehistoric animals – for obvious reasons:

“It’s a demonstration of evolution,” said Larsson, who has studied bird evolution for the last 10 years.

“If I can demonstrate clearly that the potential for dinosaur anatomical development exists in birds, then it again proves that birds are direct descendants of dinosaurs.”

“We’re not going to hatch a T. rex or something,” Larsson chuckles.

The idea came to him after meeting Jack Horner, author of the book “How to Build A Dinosaur” and the technical advisor behind the Hollywood version of Jurassic Park.

Come back to the Friday Science Review (perhaps in a few years) for an update on the “chickensaurus” experiment…

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