Motor protein that blocks ovarian tumor growth found
Washington: Penn State College of Medicine researchers have discovered that a motor regulatory protein could block human ovarian tumor growth, leading to eventual cancer cell death and possible new therapies to treat the disease.
Previously, Prof Kathleen M. Mulder, along with her colleagues, learned that km23-1 -- a protein -- is defective in nearly half of all ovarian cancer patients.
In the current study, the 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," said Mulder.
"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," she added.
"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," said Nageswara Pulipati, a postdoctoral fellow in Mulder``s lab.
"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, 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," said Mulder.
"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," she added.
The findings will appear in an upcoming edition of The International Journal of Cancer.