Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Events

05 Mar 2017 - 09 Mar 2017
20 Mar 2017 - 23 Mar 2017
12 Apr 2017 - 14 Apr 2017

BRAF Mutation Triggers Series of Cellular Transformations Leading to Colon Cancer

By BiotechDaily International staff writers
Posted on 23 Jul 2013
ADVERTISEMENT
SARTORIUS AG
Cancer researchers have found that the activity of the protein encoded by the mutant BRAFV600E gene triggers a series of transformations (hyperplasia to adenoma to carcinoma) that convert normal cells in the colon into a precancerous and ultimately fully cancerous state.

The BRAF (v-Raf murine sarcoma viral oncogene homolog B1) gene encodes the protein serine/threonine-protein kinase B-Raf. About half of melanomas express the BRAFV600E mutation (at amino acid position number 600 on the B-Raf protein, the normal valine is replaced by glutamic acid). Inhibitors of B-Raf such as vemurafenib have been approved for the treatment of metastatic melanoma since August 2011. In addition to melanoma, this mutation has been widely observed in papillary thyroid carcinoma and colorectal cancer.

An international team of investigators performed genetic and functional analyses in mice that revealed a series of stage-specific molecular alterations driving different phases of tumor evolution and uncovered mechanisms underlying this stage specificity. They reported in the July 8, 2013, issue of the journal Cancer Cell that BRAFV600E expression was sufficient for hyperplasia induction, but later stage intensified MAPK (mitogen-activated protein kinase)-signaling was required to drive both tumor progression and activation of intrinsic tumor suppression.

"Understanding the genetic makeup of different colorectal cancer subtypes will guide therapeutic decision making in the future," said senior author Dr. Allan Bradley, head of the mouse genomics team at the Wellcome Trust Sanger Institute (Hinxton, United Kingdom). "Our ability to engineer specific genetic alterations in mice allows us to study the function of cancer genes and to model specific cancer subtypes at an organismal level. Such mouse models are also invaluable for testing anticancer drugs before using them in clinical trials.”

"Our approach encapsulates the aim of cancer genomics: to discover changes to DNA responsible for cancer development and pinpoint the "Achilles heels" of cancer in order to identify new treatments," said first author Dr. Roland Rad, professor of translational oncology at the Technical University of Munich (Germany). "Our studies in mice revealed how genes cooperate to cause a specific subset of colon cancers. We identified main players, the order in which they occur during tumor progression, and the molecular processes how they turn relatively benign cell growth into threatening cancers. Such processes are targets for new treatments."

Related Links:

Wellcome Trust Sanger Institute
Technical University of Munich



Channels

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Business

view channel

Collaborative Agreement to Aid in Setting Guidelines for Evaluating Potential Ebola Therapy

Cooperation between an Israeli biopharmaceutical company and medical branches of the US government is designed to set ground rules for continued evaluation of an experimental therapy for Ebola virus disease. RedHill Biopharma Ltd. (Tel Aviv, Israel), a biopharmaceutical company primarily focused on development and c... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.