Genetic pathway can slow spread of ovarian cancer

by David Ellis
Intermediate magnification micrograph of a low malignant potential (LMP) mucinous ovarian tumour. H&E stain. The micrograph shows: Simple mucinous epithelium (right) and mucinous epithelium that pseudo-stratifies (left - diagnostic of a LMP tumour). Epithelium in a frond-like architecture is seen at the top of image. Credit: Nephron /Wikipedia. CC BY-SA 3.0

(Medical Xpress)—University of Adelaide research into the origins of ovarian cancer has led to the discovery of a genetic pathway that could slow the spread of the cancer.

The discovery is in part due to research into the genetics of humans' most distant mammalian relative, the platypus.

In a paper published today in the journal PLOS ONE, researchers characterise a - involving piRNA genes - that is turned on in .

"This pathway is important for the development of the ovaries in drosophila flies but little is known about its role in the mammalian ovary," says lead author Associate Professor Frank Grützner, Genetics Lecturer and ARC Research Fellow with the University of Adelaide's Robinson Research Institute and the School of Molecular and Biomedical Science.

"We previously found that these genes are active in cells supporting oocyte (egg cell) development in platypus, mice and humans, just like in flies.

"We then decided to look into ovarian cancer and discovered that expression of these genes is turned up in this disease. We expected that these genes would promote the spreading of cancer cells but when we switched them on in ovarian cancer cell lines in the laboratory we observed the contrary, a suppression of spread.

"This result was very surprising, and we therefore looked back at the cancers and found that many RNAs, produced from one of the genes, are faulty," Associate Professor Grützner says. "There have been previous studies in other cancers that have shown these genes actually increase growth and spread of cancer. We are only beginning to understand how this pathway might work in cancer and this work shows that it may act in completely different ways depending on the type of cancer. It also shows that these genes might be switched on in cancer but don't function properly."

The research team, involving University of Adelaide Professor Martin K. Oehler, Director of Gynaecological Oncology at the Royal Adelaide Hospital, believes a mutation in this genetic pathway could promote the spread of ovarian cancer in patients.

"The laboratory tests have been conclusive that the intact gene prevents the spread of ovarian cancer. If we're able to better understand what's preventing these from functioning normally, this could be of significant interest for further research," Professor Oehler says.

"Ovarian cancer is the most lethal gynaecological cancer world wide, and a better understanding of the molecular mechanisms responsible for its origin and progression are warranted to improve patient survival."

Associate Professor Grützner says this research is an example of how basic science comparing species as different as platypus and humans can make significant contributions to the understanding of human disease.

More information: Lim SL, Ricciardelli C, Oehler MK, De Arao Tan IMD, Russell D, et al. (2014) Overexpression of piRNA Pathway Genes in Epithelial Ovarian Cancer. PLoS ONE 9(6): e99687. DOI: 10.1371/journal.pone.0099687

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