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RNA splicing factor implicated in ovarian tumor cell growth

April 10, 2007

An RNA-binding protein that is overproduced in ovarian cancer may present a new target for diagnosis or treatment of ovarian and other cancers, according to researchers at the University of Illinois at Chicago.

Researchers in the UIC College of Pharmacy found that interfering with the production of a splicing factor can inhibit the growth and invasiveness of tumor cells in test-tube experiments.

"In a previous study, we observed that human ovarian tumors overexpressed polypyrimidine tract-binding protein, or PTB, and another splicing factor compared to normal matching ovarian tissues," said William Beck, professor and head of biopharmaceutical sciences.

In the new study, Beck and research assistant professor Xiaolong He show that knocking down PTB expression with small, interfering RNA "substantially impairs ovarian tumor cell growth, colony formation and invasiveness."

The research has been published in the online version of the journal Oncogene; it will appear in an upcoming issue of the journal's print version.

Ovarian cancer is commonly referred to as "the silent killer," as it usually is not discovered until its advanced stages. If diagnosed and treated while the cancer is confined to the ovary, the 5-year survival rate is more than 90 percent, according to the American Cancer Society. Unfortunately, only 19 percent of all cases are found in the early stages.

One woman in 58 will develop ovarian cancer during her lifetime, the American Cancer Society said. In 2006, it was estimated that there were 20,180 new cases of ovarian cancer; 15,310 women were expected to die from the disease.

"Ovarian cancer is the deadliest disease among all gynecological cancers," said He. "Two factors account for the dismal mortality outcomes. One is the absence of reliable early detection markers, and the other is inadequacy of present therapy for advanced disease. To improve patient survival, it is critical to identify new biomarkers for early detection."

Polypyrimidine tract-binding protein is a key regulator of splicing, Beck said. Defects in pre-messenger RNA splicing have been shown to cause a variety of human diseases. Evidence suggests that altered splicing is associated with and possibly involved in tumor progression or metastasis.

"To the best of our knowledge, this is the first time anyone has shown that interference with the production of a splicing factor can inhibit tumor cell growth and tumor invasiveness," Beck said. "Alternatively-spliced genes and splicing factors are likely to play a key role as therapeutic targets and diagnostic markers in the next decade."

University of Illinois at Chicago