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EP522 Changes in transcriptional activity of apoptosis-regulating genes associated with age and endometrial cancer grade
  1. E Frantsiyants,
  2. T Moiseenko,
  3. I Kaplieva,
  4. V Bandovkina,
  5. A Menshenina,
  6. M Adamyan,
  7. E Verenikina and
  8. T Myagkova
  1. Rostov Research Institute of Oncology, Rostov-on-Don, Russian Federation


Introduction/Background Paradoxically, endometrial tumors demonstrate a significant increase in apoptosis correlating with the disease progression and a poor prognosis. The purpose of the study was to analyze intact and pathological uterine tissues for the relative expression of genetic loci involved in the regulation of signaling pathways of the apoptosis development.

Methodology Biopsy tissues (tumor and intact) of the uterus from 27 patients aged 38–72 years with endometrial cancer (EC) were studied. Relative expression of 9 genetic loci involved in the regulation of signaling pathways of the apoptosis development (BAX, CASP7, CASP3, CASP8, CASP9, CASP8/FADD, p53, MDM2 and BCL2) was determined by RT-qPCR.

Results Patients with G1 EC (45–68 years) showed elevated expression of both pro-apoptotic genes CASP3, CASP9, and p53 by 222%, 131% and 98% respectively (p<0.05), and anti-apoptotic genes MDM2 (by 80%) and BCL2 (by 100%) in tumor tissues. Expression of the anti-apoptotic BAX gene was increased by 79% (p<0.005) in patients with G2 EC (38–69 years). In patients with G3 EC (55–63 years), significant (p<0.005) increase in expression of pro-apoptotic genes CASP7, CASP3, CASP8 and p53 by 71%, 90%, 53% and 150% respectively was noted together with decreased expression of the anti-apoptotic c-FLIP gene by 10% in tumor tissues (p<0.05).

Conclusion The results showed that some characteristics of expression of pro- and anti-apoptotic genetic loci in uterine malignancies were associated with age of patients and tumor grades. G1 EC demonstrated simultaneously elevated expression of pro-apoptotic (CASP3, CASP9, p53) and anti-apoptotic genes (MDM2, BCL2), while in G2 and G3 EC, pro-apoptotic genes (BAX, CASP7, CASP3, CASP8) increased with the inhibition of transcriptional activity of the anti-apoptotic c-FLIP gene neutralizing an external pathway for the apoptosis initiation through the activation of death receptors.

Disclosure Nothing to disclose.

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