Researchers at The University of Texas M. D. Anderson Cancer Center have discovered a potential oncogene in ovarian cancer, which is the leading cause of gynecological cancer death in women.

They say that levels of the protein produced by this suspected oncogene, known as atypical protein kinase C iota ( PKCi ), in combination with a second protein, Cyclin E, strongly predict outcome in non-serous ovarian cancer, which accounts for 40 percent of ovarian cancer cases.

PKCi is over-expressed in serous ovarian cancer, which makes up the remaining 60 percent of ovarian cancer cases.

Based on these findings, published in the Proceedings of the National Academy of Sciences ( PNAS ), the researchers suggest that PKCi as well as the second protein, Cyclin E, could be used as a powerful predictive test for non-serous ovarian cancer.

An agent that inhibits PKCi might offer a novel therapy for both forms of the cancer, which is difficult to treat in advanced stages.

This study is the first to find that PKCi plays a role in ovarian cancer, says the study's principal investigator Gordon Mills.

Mills and the research team, which includes investigators from Lawrence Berkeley National Laboratory and the University of Wisconsin, believe that over-expression of PKCi triggers excess production of Cyclin E, which is known to play a role in cancer growth.

PKCi is a member of a family of PKC kinase proteins that regulates cell-to-cell communication and spatial orientation. While some members of this large family have been associated with cancer, PKCi had not before this study.

PKCi and Cyclin E together contribute to the aggressiveness of ovarian cancer because high levels of the protein are associated with reduced survival. " This is the strongest predictive combination of markers to determine behavior of ovarian cancer yet found," Mills says.

Studying more than 400 tumor biopsies, they found PKCi over-expression in all samples of serous ovarian cancer, and that elevated levels of PKCi and Cyclin E corresponded to a worsening prognosis in women with non-serous ovarian cancer.

Specifically, researchers found that patients with non-serous ovarian cancer whose tumor samples showed low levels of the protein had a chance of long-term survival that was greater than 85 percent. But the chance of long-term survival in patients whose cancer showed high levels of both proteins fell to less than 15 percent.

Researchers used a technique known as comparative genomic hybridization which measured changes at the DNA level globally in tumors. It reviewed and compared the human genome in normal versus cancerous cells and found an area of constant genomic change in over 200 samples of ovarian cancer. Further probing found an area on chromosome 3 that was abnormal in the majority of ovarian cancer patients, Mills says.

They identified the PKCi gene as potentially contributing to this change and then turned to a "model organism," the fruit fly, to understand why PKCi could contribute to ovarian cancer. Fruit flies are used in this kind of research, Mills says, because " 85 percent of all known human cancer genes have a corresponding gene in these organisms."

Source: University of Texas M. D. Anderson Cancer Center, 2005


XagenaMedicine2005