Oncogenic MAP2K1 mutations in human epithelial tumors

Carcinogenesis
Young Lim ChoiHiroyuki Mano

Abstract

The scirrhous subtype of gastric cancer is a highly infiltrative tumor with a poor outcome. To identify a transforming gene in this intractable disorder, we constructed a retroviral complementary DNA (cDNA) expression library from a cell line (OCUM-1) of scirrhous gastric cancer. A focus formation assay with the library and mouse 3T3 fibroblasts led to the discovery of a transforming cDNA, encoding for MAP2K1 with a glutamine-to-proline substitution at amino acid position 56. Interestingly, treatment with a MAP2K1-specific inhibitor clearly induced cell death of OCUM-1 but not of other two cells lines of scirrhous gastric cancer that do not carry MAP2K1 mutations, revealing the essential role of MAP2K1(Q56P) in the transformation mechanism of OCUM-1 cells. By using a next-generation sequencer, we further conducted deep sequencing of the MAP2K1 cDNA among 171 human cancer specimens or cell lines, resulting in the identification of one known (D67N) and four novel (R47Q, R49L, I204T and P306H) mutations within MAP2K1. The latter four changes were further shown to confer transforming potential to MAP2K1. In our experiments, a total of six (3.5%) activating mutations in MAP2K1 were thus identified among 172 of specimens or cell line...Continue Reading

References

Sep 1, 1995·Molecular and Cellular Biology·D BottorffJ C Stone
Apr 16, 1998·Nature·P GuilfordA E Reeve
Dec 15, 2000·Oncogene·S G Rane, E P Reddy
Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
Dec 2, 2004·Nature Reviews. Cancer·Judith S Sebolt-Leopold, Roman Herrera
Aug 9, 2006·Nature Clinical Practice. Oncology·I Bernard Weinstein, Andrew K Joe
Mar 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tammie C YehEli Wallace
Jun 24, 2008·Nature Reviews. Molecular Cell Biology·Antoine E Karnoub, Robert A Weinberg
Dec 6, 2008·Nature Medicine·Julian Downward
Jan 22, 2009·European Journal of Human Genetics : EJHG·Maria Lisa DenticiBruno Dallapiccola
Sep 8, 2010·The New England Journal of Medicine·Keith T FlahertyPaul B Chapman
Oct 29, 2010·The New England Journal of Medicine·Eunice L KwakA John Iafrate
Oct 29, 2010·The New England Journal of Medicine·Young Lim ChoiUNKNOWN ALK Lung Cancer Study Group
Feb 1, 2011·The Lancet Oncology·William Pao, Nicolas Girard

❮ Previous
Next ❯

Citations

Jan 20, 1998·Biochimica Et Biophysica Acta·D F Cunningham, B O'Connor
Jun 20, 2012·Nature Reviews. Gastroenterology & Hepatology·Mert ErkanHelmut Friess
May 9, 2016·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Galia Maik-Rachline, Rony Seger
Aug 15, 2015·Annual Review of Biomedical Engineering·Julio Saez-RodriguezSimon Cook
Nov 30, 2013·Genomics, Proteomics & Bioinformatics·Mahmoud ElHefnawiMarwa Amer
Jun 18, 2016·Frontiers in Oncology·Markus Hartl
Oct 8, 2019·Genes, Chromosomes & Cancer·Danielle C Costigan, Fei Dong
Dec 7, 2019·The European Respiratory Journal·Fanélie JouenneAbdellatif Tazi
Jul 1, 2019·Journal of Clinical Pathology·Mads Rohde HarthimmerSönke Detlefsen
Jul 12, 2013·Oncology Reports·Kazutaka FukumuraHiroyuki Mano
Oct 30, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maria E ArcilaMarc Ladanyi
Sep 26, 2014·Molecular Cancer Therapeutics·Shunsuke SogabeKazuto Nishio

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.