Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
JIB
GLOBETECH PUBLISHING

Loss of Specific MicroRNA Spurs Drug Resistance in Breast Cancer Cells

By BiotechDaily International staff writers
Posted on 17 May 2012
A study determined that development of resistance to the chemotherapeutic drug tamoxifen by breast tumors was due to the disappearance of a specific microRNA.

MicroRNAs are snippets of about 20 nucleotides that block gene expression by attaching to molecules of messenger RNA (mRNA) in a fashion that prevents them from transmitting the protein synthesizing instructions they had received from the DNA.

In the study, investigators at the German Cancer Research Center (Heidelberg, Germany) related genome-wide miRNA microarray analyses of breast tumors to the appearance in the tumors of resistance to tazmoxifen.

They reported in the April 16, 2012, online edition of the journal Oncogene that the microRNA miRNA-375 was among the top downregulated miRNAs in resistant cells. Reexpression of miR-375 was sufficient to resensitize tumor cells to tamoxifen and partly reversed the epithelial–mesenchymal transition (EMT), which is characteristic of tumor cells.

A combination of mRNA profiling, bioinformatics analysis, and experimental validation identified the protein metadherin (MTDH) as a direct target of miR-375. Metadherin is an oncogenic protein that is normally blocked by miR-375. The importance of MTDH was confirmed in experiments with tumor cells that lacked the MTDH gene. In these tumors, even in the absence of miR-375, no resistance to tamoxifen arose.

“The analysis of microRNAs in breast cancer has put us on the track of metadherin. We will possibly be able to specifically influence the cancer-promoting properties of this protein in the future,” said coauthor Dr. Stefan Wiemann, associate professor of molecular genome analysis at the German Cancer Research Center. “Resistances to drugs are the main reason why therapies fail and disease progresses in many cancers. We want to understand what goes on in the cells when this happens so we can develop better therapies in the future.”

Related Links:

German Cancer Research Center



comments powered by Disqus

Channels

Drug Discovery

view channel
Image: Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells (Photo courtesy of the University of Texas, Austin).

Experimental Drug Kills Cancer Cells by Interfering with Their Ion Transport Mechanism

An experimental anticancer drug induces cells to enter a molecular pathway leading to apoptosis by skewing their ion transport systems to greatly favor the influx of chloride anions. To promote development... Read more

Therapeutics

view channel
Image: Liver cells regenerated in mice treated with a new drug (right) compared with a control group (center) after partial liver removal. Healthy liver cells are shown at left (Photo courtesy of Marshall et al, 2014, the Journal of Experimental Medicine).

New Drug Triggers Liver Regeneration After Surgery

Investigators have revealed that an innovative complement inhibitor decreases complement-mediated liver cell death, and actually stimulates postsurgery liver regrowth in mice. Liver cancer often results... Read more

Business

view channel

Partnership Established to Decode Bowel Disease

23andMe (Mountain View, CA,USA), a personal genetics company, is collaborating with Pfizer, Inc. (New York, NY, USA), in which the companies will seek to enroll 10,000 people with inflammatory bowel disease (IBD) in a research project designed to explore the genetic factors associated with the onset, progression, severity,... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.