Among U.S. women, an estimated 21,880 new cases and 13,850 deaths occurred in 2010 from epithelial ovarian cancer, one of the most common forms of ovarian cancer and the most lethal gynecologic cancer in women.
Previously, Kathleen M. Mulder, Ph.D., professor, biochemistry and molecular biology, along with members of her laboratory, learned that km23-1 -- a protein -- is defective in nearly half of all ovarian cancer patients. In the current study, researchers induced over-expression of km23-1 in human ovarian cancer cells placed in mice, causing the cells to produce large amounts of the normal protein.
km23-1 is a subunit of dynein, a motor protein that transports cargo along paths in the cell called microtubules. The dynein motor has many jobs in the cell, including major roles in cell division.
"Although microtubule-binding agents, such as the drug paclitaxel, are being used in the treatment of ovarian cancer, drug resistance has significantly limited their efficacy," Mulder said. "It is critical to develop novel, targeted therapeutics for ovarian cancer. Motor protein regulatory agents may offer promise for providing improved efficacies with reduced side effects in the treatment of ovarian cancer and other human malignancies."
Nageswara Pulipati, Ph.D., postdoctoral fellow in Mulder's lab, said, "We used a method to cause the tumors to express high levels of normal km23-1, but only in the experimental group of mice. Compared to the control group, the tumors were much smaller when km23-1 was over-expressed."
Findings were reported online (http://onlinelibrary.wiley.com/doi/10.1002/ijc.25954/abstract) and will appear in an upcoming edition of The International Journal of Cancer.
"The dynein motor protein is needed to transport checkpoint proteins along the microtubules during mitosis. However, when km23-1 levels are high, at least one checkpoint protein, BubR1, is not transferred properly," said Qunyan Jin, M.D., research associate in Mulder's lab.
During the cell division process, several checkpoints exist where specific proteins put a hold on cell division until proper completion of a specific step can be verified. When km23-1 is over-expressed, a checkpoint is stalled during mitosis -- the stage in the cell division process that normally facilitates equal splitting of the chromosomes into two identical groups before the mother cell splits into two daughter cells.
"Normally, if everything is correct at this checkpoint, the cell then goes on to divide," Mulder said. "However, with the over-expression of km23-1, the checkpoint stays on and cell division does not proceed normally, which leads to a slow cell death."
Mulder and her lab team will now look at how the over-expression of km23-1 may be mimicked to target km23-1, using nanotechnology to deliver a drug to the cancer cells, and how this approach may possibly be used in humans.
This National Institutes of Health and the Department of Defense supported this work. Also contributing to this research were Xin Liu, Ph.D., Yan Zhao, Ph.D., Baodong Sun, M.D., Manoj K. Pandey, Ph.D., Jonathan P. Huber, Ph.D. and Wei Ding, Ph.D.
Matt Solovey | EurekAlert!
Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences