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New Research Finds Three Key Proteins in Female Fertility and Cancer Biology
Promising data for infertility and cancer research
February 21, 2019
Newly published Rutger’s research has found that three proteins Aurora kinase A (AURKA), AURKB and AURKC, regulate each other in unexpected ways in female mouse eggs. The finding brings hope to female fertility and cancer biology.
Around 30% of fertility issues originate in the woman. Issues associated with female fertility include irregular ovulation, blockages in the fallopian tubes, and abnormalities of the uterus such as fibroids and endometriosis. Some of these issues may be embedded in a woman’s genetic code and some are environmental. These finding may be associated with issues with ovulation.
Understanding Aurora Proteins
What are the Aurora Protein Functions
The mammalian genome encodes three Aurora kinase protein family members: A, B, and C. While Aurora kinase A (AURKA) and B (AURKB) are found in cells throughout the body, significant protein levels of Aurora kinase C (AURKC) are limited to cells that undergo meiosis, sperm and oocyte, or egg fertilization.
While we discovered these proteins nearly 20 years ago, little is known about the function of AURKC compared to that of the other 2 Aurora kinases. This research has revealed distinct functions of AURKC in meiosis and may aid in our understanding of why chromosome segregation during meiosis I (MI) often goes awry in oocytes or eggs.
Many cancers atypically express AURKC, but because we do not fully understand AURKC function in its normal cellular context, it is difficult to predict the biological significance of this expression on the disease. Mammalian oocytes display dynamic localization of AURKC. In oocytes, AURKC expression is also regulated temporally.
Female AURKC mice survive but are subfertile due to meiotic abnormalities and compromised embryonic development. We anticipate that as more genomes are sequenced, mutations in AURKC that alter activity in the chromosomal passenger complex (CPC) will be correlated with female infertility.
Study Next Steps
What are the next steps for these discoveries?
Study senior author Karen Schindler noted the unexpected complexity in how these proteins regulate one another does not occur in any other healthy cell type. Schindler is an associate professor who specializes in infertility research in the Department of Genetics at Rutgers University-New Brunswick.
"Our research could provide a way to diagnose and perhaps treat certain types of infertility that end in early miscarriage," said Schindler, who works in the School of Arts and Sciences. "This work also impacts cancer biology research because we suspect that the inter-protein regulation that occurs in eggs also occurs in certain types of aggressive cancers. Therefore, the findings could be useful in thinking about precision medicine treatments for cancer patients."
As an internationally recognized expert in female gamete (egg) biology, Schindler explains she specializes in infertility research because she's fascinated by the surprisingly high frequency of infertility worldwide. In the US alone, one in six couples struggle with infertility.
For reproductive biology the next steps include studying the genomes of infertile patients to determine if mutations in their genes represent a significant percentage of the patient population with poor outcomes in an in vitro fertilization (IVF) clinic. For cancer biology the next steps are carefully evaluating cancers that have all three proteins and finding ways to harness their interactive regulation into a cancer treatment.
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