Navigation Links
Taking a hit or 2
Date:8/6/2012

Despite a huge amount of research effort, the molecular mechanisms that underlie the transition from a "normal" cell to a cancerous cell are only poorly understood. After the discovery of the first cancer-causing genes or oncogenes and the finding that they are mutated forms of normal cellular genes, it was widely believed that a single mutation was enough to cause cancer. Subsequent research, however, has revealed that most cancers only develop as a result of several mutations. A bewildering variety of combinations of mutations have been shown to have the potential to give rise to cancer. Finding out which combinations are dangerous has to date been largely a matter of trial and error but this should change with the development of a tool to identify mutations that really do collaborate to cause cancer. Robert Eferl and colleagues announce the new "Multi-Hit" mouse in the current issue of the journal "Nature Methods". The work is one result of a longstanding collaboration between many institutions in the Vienna area coordinated by Mathias Mller of the University of Veterinary Medicine, Vienna.

It is now generally accepted that cancer only arises if two or more genes are mutated. To date, learning which combinations of mutations cause cancer has represented an extremely laborious endeavour but the development of the "Multi-Hit" mouse looks set to change this. The group of Robert Eferl at the Ludwig Boltzmann Institute for Cancer Research, Vienna has taken advantage of the Cre-recombinase system to generate random combinations of correctly and incorrectly oriented oncogenes (or tumour suppressor genes, genes whose inactivation may contribute to the development of cancer) and investigated which of the combinations caused tumours.

They tested their system on the well-known Ras protein, which has been shown to be mutated in many different cancers. Ras mutations were thought to cause cancer only if the so-called Raf gene was also mutated but it has more recently been proposed that changes in other genes, such as those encoding the RALGEF (Ral guanine nucleotide exchange factor), MAPK (mitogen-activated protein kinase) or PI3K (phosphatitylinositol-3-kinase) proteins, may also combine with mutated Ras proteins to cause tumour development. The researchers found that mutations in Ras alone did not cause tumours to develop, while following activation of the Cre recombinase (and thus random activation by flipping of the genes under study) all mice developed cancer.

Examination of the tumours showed that in most of them all three genes had been activated, although activation of the P13K gene alone (and in very rare cases of one of the other two genes alone) could also give rise to cancer. In other words, the most rapidly proliferating, and thus most life-threatening, tumours were associated with activation of all three of the genes investigated. This indicates that all the genes are somehow contributing to the development of cancer, which means that drugs targeting any or all of them could play a part in treatment.

Eferl, now at the Institute for Cancer Research & Comprehensive Cancer Center of the Medical University of Vienna, is naturally excited by the results. "Our work on Ras has given important clues to possible therapeutic strategies. But this was really only a proof-of principle. More importantly, the results show that our Multi-Hit mouse can indeed be used to study interactions between gene mutations. This should make it much easier for us to understand how cancer arises and what we can do to treat it."


'/>"/>
Contact: Prof. Mathias Mller
mathias.mueller@vetmeduni.ac.at
43-125-077-5620
University of Veterinary Medicine -- Vienna
Source:Eurekalert

Related biology news :

1. Taking Americas rarest snake back to the woods
2. Young researcher taking fight against global killer to the next level in Vietnam
3. An invasive Asian fly is taking over European fruit
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/20/2017)... Pa. , March 20, 2017 PMD ... 2.0 personal spirometer and Wellness Management System (WMS), a ... Founded in 2010, PMD Healthcare is a Medical ... with a mission dedicated to creating innovative solutions that ... life. With that intent focus, PMD developed the first ...
(Date:3/13/2017)... HAMBURG, Germany , March 13, 2017 Future of ... ... DERMALOGs Face Matching enables to match ... characteristics forms the basis to identify individuals. (PRNewsFoto/Dermalog Identification Systems) ... DERMALOG,s "Face Matching" is the fastest software for ...
(Date:3/9/2017)... MOUNTAIN VIEW, Calif. , March 9, 2017 ... and 23andMe , the leading personal genetics company, ... Zipongo can now provide customers with personalized nutrition plans ... and biometrics, but also genetic markers impacting how their ... Zipongo,s personalized food decision support platform uses biometrics such ...
Breaking Biology News(10 mins):
(Date:3/23/2017)... PARK, Calif., March 23, 2017  BioPharmX Corporation ... products for the dermatology market, today reported financial ... 31, 2017, and will provide an update on ... the year. "We are pleased to ... year for BioPharmX," said President Anja Krammer. "We ...
(Date:3/23/2017)... 2017  Agriculture technology company Cool Planet has closed ... conversion to commercialize its Cool Terra and Cool Fauna ... products that are simultaneously profitable as well as sustainable ... 18 months. This latest round of funding was led ... The company,s primary product, Cool Terra, can ...
(Date:3/22/2017)... , March 22, 2017  Ascendis Pharma A/S ... innovative TransCon technology to address significant unmet medical ... for the full year ended December 31, 2016. ... for our company as we broadened our pipeline ... integrated rare disease company with an initial focus ...
(Date:3/22/2017)... , March 22, 2017 ... fragmented, states a research report by Transparency Market Research ... Inc., Amgen Inc., and AbbVie Inc., accounted for a ... The prominent players in this market are focusing aggressively ... product portfolio, which is likely to lead to market ...
Breaking Biology Technology: