Lack of tumor suppressor gene rb2/p130 could be an early indicator of prostate cancer, say Temple Univ. researchers

The progressive lack of the tumor suppressor gene Rb2/p130 could be an early indicator of prostate cancer in males, according to a study by researchers at Temple University’s College of Science and Technology.

The results of the study, “Expression of Cell-Cycle-regulated Proteins pRb2/p130, p107, p27kip1, p53, Mdm-2, and Ki-67 (MIB-1) in Prostatic Gland Adenocarcinoma,” appear in the June issue of Clinical Cancer Research (clincancerres.aacrjournals.org)

In the study, which was started at Thomas Jefferson University and completed at Temple’s Sbarro Institute for Cancer Research and Molecular Medicine, the researchers looked at the pattern of protein expression in a variety of molecular markers in prostate cancer, including Rb2, p107, p27, p53, Mdm-2, and Ki-67.

“The results we obtained with Rb2, which is a tumor suppressor gene, indicate that this gene demonstrates a lower expression in the prostate as it progresses from normal to cancerous,” says Antonio Giordano, Ph.D., M.D., head of the Sbarro Institute and one of the study’s lead researchers. “The lack of this tumor suppressor gene can, in a certain sense be, an indicator of tumor progression in the prostate gland.”

Giordano says the results of the study show that in addition to PSA (prostate specific antigen), a protein whose level in the blood increases in some men who have prostate cancer, there are other factors that could serve as major indicators for individuals susceptible to developing prostate cancer, which is the leading cause of death by cancer of American men.

“For the first time, we have demonstrated that there really is a link between the Rb2/p130 and prostate cancer,” says Giordano, a professor of biology at Temple. “It’s clear that this study is leading us to an early diagnostic test for cancer.”

Giordano discovered the Rb2 gene while working as a researcher at Temple’s Fels Institute for Cancer Research and Molecular Biology in the early 1990s.

“When Rb2 was discovered 10 years ago, we mapped the gene on a regional chromosome, 16q12.2,” he says. “This is very important, because in many cancer tumors–lung, prostate, ovarian and breast–there is damage in this region of the chromosome.”

Giordano says that doctors could test for the level of Rb2 expression in an individual by examining tissue samples taken from the prostate through a biopsy, but the researchers aim to develop a quick and inexpensive blood test that will yield the same results.

Giordano adds that his co-researchers are also aiming to develop a therapeutic model to re-introduce Rb2 back into the prostate. By doing so, they hope to determine if the gene is able to block the growth of cancer cells.

“It would make sense to use Rb2 as a gene therapeutic tool because it can disclose, at an earlier stage, whatever is happening in the cell cycle that is producing the cancer in the prostate,” says Giordano. “If we see there is an initial modification in a healthy prostate, toward a pre-neoplastic lesion that is going to progress to cancer, then we could reintroduce the Rb2 gene and potentially revert the situation back to normal by blocking the growth of the neoplastic cells that will eventually become cancer.”

The study, which was led by Giordano and Dr. Pier Paolo Claudio, associate professor of biology at Temple and a member of the Sbarro Institute, was an international collaborative effort, and included the Sbarro Institute, Thomas Jefferson University, MCP Hahnemann University, the University of Naples and the Cancer Institute of Naples in Italy. The National Institutes of Health and the Sbarro Health Research Organization funded the research.

“In this study, we didn’t only look at the Rb2 gene, we looked at a lot of molecular markers,” Giordano emphasizes. “We looked at all the major genes involved in carcinogenesis. And clearly, with this discovery, we were able to identify an additional mechanism in the cancer progression.”

Giordano says that the task now for researchers is to determine how genes communicate with one another in the development of cancer. “Clearly there is a ’communication’ taking place,’ he adds. “Probably it will not only be our Rb2 gene involved, but it will be like an orchestra, in which all these genes have a specific role.”

Giordano says the knowledge of how genes cooperate among themselves in the development of cancer will be “a fantastic tool” in the hands of an oncological clinician or surgeon because “it will allow them to tailor more specific therapies based on the genetic damage in each one of the genes.”