Expression of p‑Akt in ovarian serous carcinoma and its association with proliferation and apoptosis

Song,Tieying; Wang,Liwen; Mo,Zhongfu; Mao,Limei; Ma,Xiaojing; Niu,Runling; Gu,Kunfeng; Yan,Ruyu; Ma,Pengyu; Qi,Yan; Jiao,Qingfang

doi:10.3892/ol.2013.1641

Expression of p‑Akt in ovarian serous carcinoma and its association with proliferation and apoptosis

Authors:
- Tieying Song
- Liwen Wang
- Zhongfu Mo
- Limei Mao
- Xiaojing Ma
- Runling Niu
- Kunfeng Gu
- Ruyu Yan
- Pengyu Ma
- Yan Qi
- Qingfang Jiao
View Affiliations

Affiliations: Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, P.R. China, Department of Gynecology, The Sixth Hospital of Shijiazhuang, Shijiazhuang, Hebei 050000, P.R. China, Department of Neurosurgery, The First Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, P.R. China
Published online on: October 25, 2013 https://doi.org/10.3892/ol.2013.1641
Pages: 59-64

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to determine the expression of p‑Akt in ovarian serous carcinoma (OSC) and its association with proliferation and apoptosis. Paraffin‑embedded tissues of patients aged between 35 and 64 years old without history of radiotherapy, chemotherapy and hormone therapy prior to surgery were collected. In total, samples included 12 ovarian serous cystadenomas (OSAs), 18 ovarian serous borderline tumors (OS‑BTs) and 46 OSCs. Of the 46 OSC samples, 16 were well‑differentiated, 20 were moderately differentiated and 10 were poorly differentiated, while 22 developed lymphatic metastases and 24 were metastasis‑free. An additional 10 paraffin‑embedded normal ovarian tissues (NOTs) were used as controls. Streptavidin-peroxidase immunohistochemistry assays were used to investigate the expression of p‑Akt and cyclin D1 in the collected samples. Compared with NOT, p‑Akt expression in the OS‑BT and OSC groups, as well as cyclin D1 expression in the OSA and OSC groups, was significantly elevated (P<0.05). Compared with the OSA group, p‑Akt expression in the OSC group was significantly elevated (P<0.01) and reversely associated with tumor differentiation (P<0.01), whereas cyclin D1 expression showed no correlation with tumor differentiation (P>0.05). The expression of p‑Akt, caspase‑3 and cyclin D1 was positively associated with lymphatic metastasis (r=0.334; P=0.023). The expression of p‑Akt gradually increased with carcinoma development and was associated with differentiation and metastasis of OSC, revealing that the activation of the PI3K/Akt signaling pathway is involved in the development of OSC. Furthermore, the expression of cyclin D1 gradually increased in the NOT, OSA, OS‑BT and OSC groups and was associated with tumor metastasis.

View Figures

View References

1	Mooney SJ, Winner M, Hershman DL, et al: Bowel obstruction in elderly ovarian cancer patients: a population-based study. Gynecol Oncol. 129:107–112. 2013. View Article : Google Scholar : PubMed/NCBI
2	Oberaigner W, Minicozzi P, Bielska-Lasota M, et al: Survival for ovarian cancer in Europe: the across-country variation did not shrink in the past decade. Acta Oncol. 51:441–453. 2012. View Article : Google Scholar
3	Saldanha SN and Tollefsbol TO: Pathway modulations and epigenetic alterations in ovarian tumorbiogenesis. J Cell Physiol. Sep 16–2013.(Epub ahead of print).
4	Touma R, Kartarius S, Harlozinska A, Götz C and Montenarh M: Growth inhibition and apoptosis induction in ovarian cancer cells. Int J Oncol. 29:481–488. 2006.PubMed/NCBI
5	Staal SP: Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci USA. 84:5034–5037. 1987. View Article : Google Scholar : PubMed/NCBI
6	Bellacosa A, Kumar CC, Di Cristofano A and Testa JR: Activation of AKT kinases in cancer: implications for therapeutic targeting. Adv Cancer Res. 94:29–86. 2005. View Article : Google Scholar : PubMed/NCBI
7	Wang Y, Helland A, Holm R, Kristensen GB and Børresen-Dale AL: PIK3CA mutations in advanced ovarian carcinomas. Hum Mutat. 25:3222005. View Article : Google Scholar : PubMed/NCBI
8	Comstock CE, Revelo MP, Buncher CR and Knudsen KE: Impact of differential cyclin D1 expression and localisation in prostate cancer. Br J Cancer. 96:970–979. 2007. View Article : Google Scholar : PubMed/NCBI
9	Liao DJ, Thakur A, Wu J, Biliran H and Sarkar FH: Perspectives on c-Myc, Cyclin D1, and their interaction in cancer formation, progression and response to chemotherapy. Crit Rev Oncog. 13:93–158. 2007. View Article : Google Scholar : PubMed/NCBI
10	Meng Q, Xia C, Fang J, Rojanasakul Y and Jiang BH: Role of PI3K and AKT specific isoforms in ovarian cancer cell migration, invasion and proliferation through the p70S6K1 pathway. Cell Signal. 18:2262–2271. 2006. View Article : Google Scholar : PubMed/NCBI
11	Datta SR, Dudek H, Tao X, et al: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 91:231–241. 1997. View Article : Google Scholar
12	Kane LP, Shapiro VS, Stokoe D and Weiss A: Induction of NF-kappaB by the Akt/PKB kinase. Curr Biol. 9:601–604. 1999. View Article : Google Scholar : PubMed/NCBI
13	Fang X, Yu SX, Lu Y, et al: Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A. Proc Natl Acad Sci USA. 97:11960–11965. 2000. View Article : Google Scholar
14	Philp AJ, Campbell IG, Leet C, et al: The phosphatidylinositol 3′-kinase p85alpha gene is an oncogene in human ovarian and colon tumors. Cancer Res. 61:7426–7429. 2001.
15	Noske A, Kaszubiak A, Weichert W, et al: Specific inhibition of AKT2 by RNA interference results in reduction of ovarian cancer cell proliferation: increased expression of AKT in advanced ovarian cancer. Cancer Lett. 246:190–200. 2007. View Article : Google Scholar
16	Malumbres M and Barbacid M: Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 9:153–166. 2009. View Article : Google Scholar : PubMed/NCBI
17	Sherr CJ: Mammalian G1 cyclins. Cell. 73:1059–1065. 1993. View Article : Google Scholar : PubMed/NCBI
18	Lee SH, Lee JK, Jin SM, et al: Expression of cell-cycle regulators (cyclin D1, cyclin E, p27kip1, p57kip2) in papillary thyroid carcinoma. Otolaryngol Head Neck Surg. 142:332–337. 2010. View Article : Google Scholar : PubMed/NCBI
19	Maurer U, Charvet C, Wagman AS, Dejardin E and Green DR: Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Mol Cell. 21:749–760. 2006. View Article : Google Scholar
20	Robey RB and Hay N: Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene. 25:4683–4696. 2006. View Article : Google Scholar
21	Dummler B and Hemmings BA: Physiological roles of PKB/Akt isoforms in development and disease. Biochem Soc Trans. 35:231–235. 2007. View Article : Google Scholar : PubMed/NCBI
22	Manning BD and Cantley LC: AKT/PKB signaling: navigating downstream. Cell. 129:1261–1274. 2007. View Article : Google Scholar : PubMed/NCBI
23	Dey A, Tergaonkar V and Lane DP: Double-edged swords as cancer therapeutics: simultaneously targeting p53 and NF-kappaB pathways. Nat Rev Drug Discov. 7:1031–1040. 2008. View Article : Google Scholar : PubMed/NCBI