Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.4)
Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2016, vol. 25, nr 3, May-June, p. 513–521

doi: 10.17219/acem/62540

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Expression of Interactive Genes Associated with Apoptosis and Their Prognostic Value for Ovarian Serous Adenocarcinoma

Kyusik Shin1,A, Ki Hyung Kim2,*,B,C, Man Soo Yoon2,*,C,D, Dong Soo Suh2,A,D, Ji Young Lee3,B,E, Ari Kim4,A,B, Wankyu Eo5,A,B

1 Department of Medicine, Pusan National University School of Medicine, Busan, Korea

2 Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Biomedical Research Institute and Pusan Cancer Center, Pusan National University Hospital, Busan, Korea

3 Department of Obstetrics and Gynecology, College of Medicine, Konkuk University, Seoul, Korea

4 Department of Obstetrics and Gynecology, Institute of Wonkwang Medical Science, College of Medicine, Wonkwang University, Iksan, Korea

5 Department of Obstetrics and Gynecology, College of Medicine, Kyunghee University, Seoul, Korea

Abstract

Background. Malignant ovarian tumor is one of the leading causes of worldwide cancer death. It is usually characterized by insidious onset and late diagnosis because of the absence of symptoms, allowing ovarian cancer cases to progress rapidly and become unresectable. The tumor suppressor, p53, plays an important role in regulating cell cycles and apoptosis. p53 is regulated by several molecules, and it interacts with other apoptotic proteins.
Objectives. To compare the prognosis of ovarian serous carcinoma and evaluate the expression of DNA-PKcs, Akt3, GSK-3β, and p53 in cancerous cells.
Material and Methods. DNA-PKcs, Akt3, GSK-3β, and p53 expression levels were scored using immunohistochemistry staining of tissue samples from 132 women with ovarian serous adenocarcinoma. Expression was confirmed by real-time RT-PCR. Analyses were stratified by age, tumor grades, cancer stages and serum CA 125 levels.
Results. Significant differences in DNA-PKcs, Akt3, and p53 expression were observed between participants with different stages and tumor grades of ovarian serous adenocarcinoma. DNA-PKcs and p53 expression increased along with increasing tumor grade. Meanwhile, DNA-PKcs, Akt3, and p53 expression increased along with increasing cancer stage, and with a decrease in 5-year overall survival rate.
Conclusion. This study shows that elevated expression of DNA-PKcs, Akt3, and p53 in ovarian serous adenocarcinoma tissues are an indication of more advanced disease and worse prognosis.

Key words

epithelial ovarian cancer, DNA-PKcs, Akt3, GSK-3β

References (28)

  1. Siegel R, Naishadham D, Jemal A: Cancer Statistics, 2013. CA Cancer J Clin 2013, 63, 11–30.
  2. Runnebaum IB, Stickeler E: Epidemiological and molecular aspects of ovarian cancer risk. J Cancer Res Clin Oncol 2001, 127, 73–79.
  3. Park P, Jeong J, Kim S, Park J: MAD2 expression in ovarian carcinoma: Different expression patterns and levels among various types of ovarian carcinoma and its prognostic significance in high-grade serous carcinoma. Korean J Pathol 2013, 47, 418–425.
  4. Wong RS: Apoptosis in cancer: From pathogenesis to treatment. J Exp Clin Cancer Res 2011, 30, 87.
  5. Braithwaite AW, Royds JA, Jackson P: The p53 story: Layers of complexity. Carcinogenesis 2005, 26, 1161–1169.
  6. Wawrzynow B, Zylicz A, Wallace M, Hupp T, Zylicz M: MDM2 chaperones the p53 tumor suppressor. J Biol Chem 2007, 282, 32603–32612.
  7. Zhang L, Zhang J, Hu C, Cao J, Zhou X, Hu Y: Efficient activation of p53 pathway in A549 cells exposed to L2, a novel compound targeting p53-MDM2 interaction. Anticancer Drugs 2009, 20, 416–424.
  8. Boehme K, Kulikov R, Blattner C: p53 stabilization in response to DNA damage requires Akt/PKB and DNA-PK. Proceedings of the National Academy of Sciences of the United States of America 2008, 105, 7785–7790.
  9. Fulda S, Debatin KM: Apoptosis signaling in tumor therapy. Ann N Y Acad Sci 2004, 1028, 150–156.
  10. Fadeel B, Orrenius S: Apoptosis: A basic biological phenomenon with wide-ranging implications in human disease. J Intern Med 2005, 258, 479–517.
  11. Ashkenazi A: Directing cancer cells to self-destruct with pro-apoptotic receptor agonists. Nat Rev Drug Discov 2008, 7, 1001–1012.
  12. Pflaum J, Schlosser S, Muller M: p53 Family and Cellular Stress Responses in Cancer. Front Oncol 2014, 4, 285.
  13. Wu J, Li QQ, Zhou H, Lu Y, Li JM, Ma Y: Selective tumor cell killing by triptolide in p53 wild-type and p53 mutant ovarian carcinomas. Med Oncol 2014, 31, 14.
  14. Duffy MJ, Synnott NC, McGowan PM, Crown J, O’Connor D, Gallagher WM: p53 as a target for the treatment of cancer. Cancer Treat Rev 2014, 40, 1153–1160.
  15. Brooks CL, Gu W: p53 ubiquitination: Mdm2 and beyond. Mol Cell 2006, 21, 307–315.
  16. Feng Z, Levine AJ: The regulation of energy metabolism and the IGF-1/mTOR pathways by the p53 protein. Trends Cell Biol 2010, 20, 427–434.
  17. Liu J, Zhang C, Feng Z: Tumor suppressor p53 and its gain-of-function mutants in cancer. Acta Biochim Biophys Sin (Shanghai) 2014, 46, 170–179.
  18. Green DR, Kroemer G: Cytoplasmic functions of the tumour suppressor p53. Nature 2009, 458, 1127–1130.
  19. Kimmelman AC: The dynamic nature of autophagy in cancer. Genes Dev 2011, 25, 1999–2010.
  20. Criollo A, Senovilla L, Authier H, Maiuri MC, Morselli E, Vitale I: IKK connects autophagy to major stress pathways. Autophagy 2010, 6, 189–191.
  21. Muller PA, Vousden KH: p53 mutations in cancer. Nat Cell Biol 2013, 15, 2–8.
  22. Sipley JD, Menninger JC, Hartley KO, Ward DC, Jackson SP, Anderson CW: Gene for the catalytic subunit of the human DNA-activated protein kinase maps to the site of the XRCC7 gene on chromosome 8. Proc Natl Acad Sci U S A 1995, 92, 7515–7519.
  23. Hammarsten O, DeFazio LG, Chu G: Activation of DNA-dependent protein kinase by single-stranded DNA ends. J Biol Chem 2000, 275, 1541–1550.
  24. Achanta G, Pelicano H, Feng L, Plunkett W, Huang P: Interaction of p53 and DNA-PK in response to nucleoside analogues: Potential role as a sensor complex for DNA damage. Cancer Res 2001, 61, 8723–8729.
  25. Wang Z, Smith KS, Murphy M, Piloto O, Somervaille TCP, Cleary ML: Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy. Nature 2008, 455, 1205–1209.
  26. Frame S, Cohen P: GSK3 takes centre stage more than 20 years after its discovery. Biochem J 2001, 359, 1–16.
  27. Turenne GA, Price BD: Glycogen synthase kinase3 beta phosphorylates serine 33 of p53 and activates p53’s transcriptional activity. BMC Cell Biol 2001, 2, 12.
  28. Kulikov R, Boehme KA, Blattner C: Glycogen synthase kinase 3-dependent phosphorylation of Mdm2 regulates p53 abundance. Mol Cell Biol 2005, 25, 7170–7180.
© Wroclaw Medical University