A two-pronged attack: Why loss of STAT1 is bad news
Breast cancer represents about a fifth of all cancers diagnosed in women. The reasons for the rapid progression of the disease remain relatively poorly understood but recent work in the group of Veronika Sexl at the University of Veterinary Medicine, Vienna has pointed the finger strongly at loss or inactivation of the transcription factor STAT1. The results are published in the current issue of the journal Oncotarget.
The so-called signal transducers and activators of transcription (STATs) are involved in the regulation of cell division but details of their functions remain a matter of conjecture. In the development of breast cancer, the role of STAT1 is particularly interesting as high levels of STAT1 activity are known to be correlated with a better prognosis for breast cancer patients. There is a considerable body of evidence that STAT1 can act to suppress tumour growth in breast cancer but how does it function? Important clues are provided by the latest results of Christine Schneckenleithner and colleagues in the group of Veronika Sexl at the Vetmeduni Vienna.
By means of a series of sophisticated transplantation experiments in a mouse model, Schneckenleithner was able to show that in the absence of the STAT1 protein the mouse develops breast cancer more frequently, partly because the animal's immune system loses the ability to control developing tumours. Under normal circumstances, i.e. in the presence of STAT1, a type of white blood cells known as cytotoxic T lymphocytes or CTL recognizes and kills developing tumours as part of the body's normal tumour surveillance mechanism. In the absence of STAT1, however, the CTL can no longer perform this essential function, allowing cancer cells to grow unchecked (the other mechanism for killing tumour cells, involving "natural killer" cells, was found to play at best a very minor part in destroying breast cancer cells, at least in this model system).
The loss of susceptibility to CTL enables tumour cells to grow unimpeded. But Schneckenleithner's work also uncovered a further way in which STAT1 helps keep breast cancer in check. When the protein is removed from breast cells, there is an increased formation of small cancerous growths within the epithelia, known as mammary intraepithelial neoplasias or MINs. MINs arise as a result of accelerated cell division within the epithelial cells and are believed to represent a stepping-stone on the way to full-blown cancer. In other words, removing STAT1 is somehow interfering with a mechanism presumably involving the transcription factor IRF1, which is known to be under the direct control of STAT1 for preventing unwanted cell division.
The loss of STAT1 thus causes the development of breast cancer via two mechanisms. Schneckenleithner summarizes the problem very neatly: "not only does deleting STAT1 cause the mice to develop more mini-cancers, it also prevents the main mechanism by which these are destroyed, leading to much faster tumour development." This double effect explains why the prognosis for breast cancer patients with low activities of STAT1 is so poor and also points the way towards a possible treatment for this most widespread of cancers.
More information: The scientific article in full text online: www.impactjournals… 1&path=625
Provided by University of Veterinary Medicine -- Vienna
- Milk thistle extract stops lung cancer in mice Nov 15, 2011 | not rated yet | 0
- The good, the bad and the ugly: The many roles of c-JUN in cancer Jun 28, 2011 | not rated yet | 0
- Silencing a deadly conversation in breast cancer Jun 02, 2011 | not rated yet | 0
- Another step toward resisting breast cancer Sep 21, 2011 | not rated yet | 0
- 'If Hamlet give the first or second hit': The development of Burkitt's lymphoma Nov 08, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
The use of a smartphone application significantly improves patients' preparation for a colonoscopy, according to new research presented today at Digestive Disease Week (DDW). The preparation process, which begins days in ...
Cancer 23 hours ago | not rated yet | 0
Research presented at Digestive Disease Week (DDW) explores new methods for managing digestive health through diet and lifestyle.
Cancer 23 hours ago | not rated yet | 1
A ground-breaking advance in colonoscopy technology signals the future of colorectal care, according to research presented today at Digestive Disease Week(DDW). Additional research focuses on optimizing the minimal withdrawal ...
Cancer May 18, 2013 | 5 / 5 (2) | 0
(HealthDay)—Concurrent use of two immune checkpoint antibodies—ipilimumab and nivolumab—may be effective for the treatment of advanced melanoma, according to a proof-of-principal study presented in ...
Cancer May 17, 2013 | not rated yet | 0
(HealthDay)—The risks of metastasis and death associated with cutaneous squamous cell carcinoma (CSCC) are low, but significant, and risk factors for poor outcome include tumor diameter, invasion beyond ...
Cancer May 17, 2013 | not rated yet | 0 |
Scientists at Johns Hopkins have turned their view of osteoarthritis (OA) inside out. Literally. Instead of seeing the painful degenerative disease as a problem primarily of the cartilage that cushions joints, ...
12 hours ago | 4.8 / 5 (4) | 0 |
In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...
12 hours ago | 5 / 5 (2) | 0 |
Researchers at the University of Wisconsin have identified a potential new risk factor for obstructive sleep apnea: asthma. Using data from the National Institutes of Health (Heart, Lung, and Blood Institute)-funded Wisconsin ...
11 hours ago | not rated yet | 0 |
A new study looking at sleep-disordered breathing (SDB) and markers for Alzheimer's disease (AD) risk in cerebrospinal fluid (CSF) and neuroimaging adds to the growing body of research linking the two.
11 hours ago | 5 / 5 (2) | 0 |
The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.
16 hours ago | not rated yet | 0
Gourmands and foodies everywhere have long recognized ginger as a great way to add a little peppery zing to both sweet and savory dishes; now, a study from researchers at Columbia University shows purified components of the ...
11 hours ago | not rated yet | 0