Potential Biomarker for Ovarian Cancer

A new study explains how alterations in the km23 protein may contribute to the development of ovarian cancer, and suggests that this protein could be exploited as a biomarker for detection of the disease.

Km23, a novel tumor growth factor (TGF)-beta signaling component that mediates growth inhibition and other TGF-beta responses, is altered in 42% of ovarian cancer patient tumors. Studies of the Drosophila homologue of km23 showed an increase in mitotic index, suggesting that km23 may function as a tumor suppressor.

Investigators at the Pennsylvania State University College of Medicine (Hershey, USA) used laser-capture microdissection and nested reverse-transcription-PCR (polymerase chain reaction), to show that km23 was altered at a high frequency in human ovarian cancer patients. No km23 alterations were detected in 15 normal tissues. These findings were published in the August 1, 2005, issue of Cancer Research.

Patients with a mutated form of km23 displayed a disruption in binding to the dynein intermediate chain, suggesting a defect in cargo recruitment to the dynein motor complex. Dynein, a microtubule-associated protein (MAP) lies at the heart of microtubule-based movement. Motor MAPs attach both to intracellular components, and to microtubules, and by moving along the microtubules they are able to transport the intracellular components, which could be organelles, or vesicles, to where they are required. This process is initiated by TGF-beta binding to receptors on the cell's surface. This, in turn, sends a signal to km23 telling it to attach to the motor and pick up the cargo. When km23 is altered, the cargo does not reach the correct destination in the cell.

"TGF-beta is a critical regulator of cell growth and is present throughout the body, explained senior author Dr. Kathleen M. Mulder, professor of pharmacology at Pennsylvania State University. "The alterations in km23 appear to disrupt some of the normal signals sent by TGF-beta. While only close to half of ovarian cancer patients may have defects in km23, our results are still highly significant because there is no clinically useful screening test available for detection of ovarian cancer.”




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