Their study, "Frequent loss of Rb2/p130 in human ovarian carcinoma," will be published in the May 1 issue of Clinical Cancer Research (http://clincancerres.
In the study, led by Antonio Giordano, M.D., Ph.D., director of the Sbarro Institute and co-director of the Center for Biotechnology at Temple, the researchers examined 45 primary ovarian carcinoma samples and found that 40 percent had a decrease or complete loss of Rb2 protein expression. Giordano discovered the Rb2 gene while working at Temple's Fels Cancer Institute in the early 1990s.
"In the samples where the protein was decreased or lost, there was an inverse correlation to the aggressiveness of the cancer," says Giuseppina D'Andrilli, Ph.D., a research fellow in the Sbarro Institute and the study's lead author. "This is consistent with the theory that if the Rb2 protein is still present in the tumor tissue, the aggressiveness of the tumor is less."
The researchers then used a viral delivery system to introduce correct copies of the Rb2 gene into the ovarian tumor cells that had shown decreased or no Rb2 protein expression.
"Introducing the gene Rb2/p130 allowed the cells to produce more proteins, and this increased protein production brought about a dramatic arrest of cells in the G1, or initial, phase of the cell cycle," says D'Andrilli.
The Temple researchers' findings were comparable to earlier studies at the Sbarro Institute in which correct copies of Rb2 were introduced into mice with lung tumors. When the Rb2 gene was over-expressed in the cancer cells, it caused the tumors in the mice to completely regress. Ovarian cancer will develop in about one out of every 57 women in the United States, according to the National Cancer Institute. Detection is often late because this type of cancer does not generally have early warning symptoms.
"This study is just one step in saying, 'OK, we have observed that the Rb2 gene has a role in ovarian carcinogenesis,'" says D'Andrilli. "We have demonstrated that it is a protein that has to be considered in the future in ovarian cancer patients."
Giordano adds that the use of Rb2 in detecting and treating ovarian cancer could have potential future clinical applications, allowing physicians to determine the aggressiveness of the cancer and to tailor specific therapies to specific patients.
"This is one more piece to understanding the complex mosaic of cancer that the researchers at the Sbarro Institute have been delicately constructing for the past decade," Giordano says.
The study was carried out at Temple's Sbarro Institute in collaboration with Temple's Fels Institute for Cancer Research, Drexel University's College of Medicine, Thomas Jefferson University, and the Catholic University of the Sacred Heart in Italy. It was funded by the National Institutes of Health and the Sbarro Health Research Organization.