Researchers have known that aggressive forms of cancer are often driven by the abnormal over-expression of cancer promoting genes, known as oncogenes. Now, scientists have identified a new gene that may contribute to aggressive breast cancer.
The research team, led by Lance Miller, Ph.D., associate professor of cancer biology at Wake Forest University School of Medicine and Bing Lim, Ph.D., of the Genome Institute of Singapore (GIS), identified a gene, known as RCP (or RAB11FIP1), that is frequently over-expressed in breast cancer and contributes to aggressive breast cancer behavior. The study was published recently in the Journal of Clinical Investigation and is available online at www.jci.org.
“We believe RCP may grease the wheels of cancer by amplifying the oncogenic signals set in motion by other molecular alterations, such as the inappropriate activation of growth-promoting receptors,” said Miller. “By shutting down RCP, we can already dramatically slow the growth and spread of some breast tumors, and perhaps by co-targeting other components of the endosomal trafficking pathway in which RCP participates, we may be able to bring the growth of some cancers to a grinding halt,” he said. Miller conducted the study while he was on the faculty of the Genome Institute of Singapore.
The GIS team initially discovered that RCP expression was positively correlated with cancer recurrence in a population of breast cancer patients. This suggested that RCP may be required by some tumors for growth and spread to other organs. When the researchers over-expressed RCP in non-cancerous breast cells, they found that RCP promotes migration, or cellular movement, which is a precursor to the ability of tumors to invade neighboring tissues. The cells take on a more aggressive behavior when over-expressed in breast cancer cells, including faster proliferation, enhanced migration/invasion and independent growth.
When the gene is silenced in breast cancer cells, the ability of the cells to form tumors and spread to other organs is greatly diminished. The researchers also found that RCP can activate the potent RAS protein, which previous research has implicated in tumor growth.
According to Miller, “One objective in my laboratory is to discover new oncogenes that drive breast cancer progression so we can devise therapeutic strategies for shutting these genes down. The involvement of RCP in breast cancer progression may have significant clinical ramifications, and we are now working towards a better understanding of its mechanism of action.”
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