A newly created mouse model of the most severe form of ovarian cancer could improve treatment options and diagnosis of the disease, according to a recent study by researchers at the University of North Carolina School of Medicine in Chapel Hill.
The research, published Jan. 27 in the journal Nature Communications, shows how two genes cooperate to trigger ovarian cancer and encourage its growth, according to a UNC School of Medicine news release. Although not all mouse models of human diseases provide an authentic picture of the human condition, the model in the study is based on genetic mutations found in human cancer sample, the news release stated. Mutations in two genes—ARID1A and PIK3CA— were previously unknown to cause cancer, the release said. The research team was led by Terry Magnuson, PhD, the Sarah Graham Kenan professor and chair of the university’s department of genetics.
“It’s an extremely aggressive model of the disease, which is how this form of ovarian cancer presents in women,” Magnuson, who also is a member of the UNC Lineberger Comprehensive Cancer Center, said in the news release.“When ARID1A is less active than normal and PIK3CA is overactive, the result is ovarian clear cell carcinoma 100 percent of the time in our model.”
Ron Chandler, PhD, a postdoctoral fellow in Magnuson’s lab, initiated the study, according to the news release. Chandler already had been studying the ARID1A gene, which normally is a gene suppressor in humans, when cancer genome sequencing projects showed the ARID1A gene was highly mutated in several types of tumors, including ovarian clear cell carcinoma, the news release said.
Researchers noted the importance of proper cell cycle regulation, pointing out that cells can become cancerous when the process goes haywire, according to the news release.
“Our research shows why we see mutations of both ARID1A and PIK3CA in various cancers, such as endometrial and gastric cancers,” Chandler said in the news release. “Too little expression of ARID1A and too much expression of PIK3CA is the perfect storm; the mice always get ovarian clear cell carcinoma. This pair of genes is really important for tumorigenesis.”
The research also found that ARID1A and PIK3CA mutations led to the overproduction of IL-6, which is a cytokine, a kind of protein that triggers inflammation. “We don’t know if inflammation causes ovarian clear cell carcinoma, but we do know it’s important for tumor cell growth,” Chandler said in the release.
Treating tumor cells with an IL-6 antibody suppressed cell growth, the news release said, and Magnuson thinks reducing IL-6 levels could help patients.
“We think that IL-6 contributes to ovarian clear cell carcinoma and could lead to death,” Magnuson said. “You really don’t want this cytokine circulating in your body.”
Read the full study at http://www.nature.com/ncomms/2015/150127/ncomms7118/full/ncomms7118.html or visit http://news.unchealthcare.org/news/2015/january/researchers-pinpoint-two-genes-that-trigger-severest-form-of-ovarian-cancer for more information.