The role of sphingolipid metabolism in Pregnancy-Associated breast cancer after chemotherapy

---

Kozyrko Elena

Research Center for Obstetrics, Gynecology and Perinatology, Russia

: J Womens Health, Issues Care

Abstract

---

Sphingolipids are now recognized as multifaceted mediators in cancer biology and therapeutics. The key role of sphingolipids in the regulation of apoptosis and cell division processes makes them important regulating compounds in cancerogenesis. Pregnancy-associated breast cancer (PABC) is the most common cancer during pregnancy, but it remains poorly studied. The aim of our study is to determine the role of sphingolipid metabolism genes, the products of which control proliferation and apoptosis, in the placenta of pregnant women with PABC after chemotherapy compared to healthy patients. Seven patients with breast cancer (BC) and eight healthy pregnant women as control group were studied. We detected (by PCR method) the expression of 15 genes of sphingolipid metabolism: sphingomyelinases (SMPD1 and SMPD3), acid ceramidase (ASAH1), glucosylceramidase (GBA), ceramide synthases (CERS 1-6), sphingosine kinase1 (SPHK1), sphingosine-1-phosphate lyase 1 (SGPL1), sphingosine-1 phosphate receptors (S1PR1, S1PR2 and S1PR3) whose enzymes control the synthesis of ceramides, sphingosines and sphingosine-1-phosphates. We found a significant increase in the expression of genes of sphingosine-1-phosphate lyase 1 SGPL1 (Ñ? = 0.04), sphingosine kinase SPHK1 (Ñ? = 0.009), ceramides synthases 1-6 CERS1 (Ñ? = 0.001), CERS2 (Ñ? = 0.004), CERS3 (Ñ? = 0.001), CERS5 (Ñ? = 0.002), CERS6 (Ñ? = 0.006) in samples of placenta of patients with PABC during their treatment with cytostatic chemotherapy. The tendency to increase of expression of ASAH gene, p = 0.09 was observed. Analysis of genes of sphingosine-1-phosphate receptors revealed increasing in expression of S1PR1, p=0.01; S1PR2, p=0.04; S1PR3, p=0.002. Our pilot study is one of the first investigating the molecular genetic characteristics of PABC. We suppose that such researches could allow identifying new targets and prognostic markers of obstetric complications, as well as opportunities to assess the effectiveness of chemotherapy in the treatment of BC during pregnancy. Significant changes in the expression of genes controlling the level of ceramides, sphingosine and S1P may indicate their promise for consideration as potential candidates for both diagnostics and therapy of patients with BC in pregnant women.

Biography

---

Elena Kozyrko has expertise in evaluation and a passion for improving womenâ??s health and reproductive potential. Her open and contextual evaluation model, based on responsive constructivists, opens up new ways to improve public health approaches to cancer pregnancy. It takes into account the interests of all stakeholders and has a different way of focusing.