Abstract
Epithelial ovarian cancer (EOC) represents the most challenging of gynecological malignancies. Defective apoptosis is a major causative factor in the development and progression of cancer. The two important pathways of apoptosis are extrinsic death receptor pathway (Fas family) and intrinsic mitochondrial pathway (Bcl-2 family). In this study, differential protein expression of the major Fas family members (Fas, FasL, and FAP-1) and Bcl-2 family members (Bax, Bcl-2, and Bcl-XL) in benign versus malignant surface epithelial ovarian tumors was evaluated at the protein level by immunohistochemistry. The expression of these molecules was compared in 30 benign versus 35 malignant surface epithelial ovarian tumors. The findings of the present study showed that there was no significant difference in the expression of the Fas family members in benign and malignant ovarian tumors. However, benign tumors showed higher levels of anti-apoptotic Bcl-2 protein levels (p < 0.009), whereas malignant tumors showed higher levels of pro-apoptotic Bax (p < 0.001). In general, there was no significant difference in Bcl-XL protein levels. The observations made in the present study suggest that alterations in expression of the Fas family and the Bcl-2 family members occur and play a key role in the deregulated growth of epithelial ovarian cancer.
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Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, Feuer EJ, Thun MJ (2004) Cancer statistics, 2004. CA Cancer J Clin 54:8–29
Seidman JD, Russell P, Kurman RJ (2002) Surface epithelial tumors of the ovary. In: Kurman RJ (ed) Blaustein’s pathology of the female genital tract, 5th edn. Springer, New York, pp 791–904
Meyer T, Rustin GJ (2000) Role of tumour markers in monitoring epithelial ovarian cancer. Br J Cancer 82:1535–1538
Reed CJ (2000) Apoptosis and cancer: strategies for integrating programmed cell death. Semin Hematol 37:9–16
Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A (2000) Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 12:611–620
Sato T, Irie S, Kitada S, Reed JC (1995) FAP-1: a protein tyrosine phosphatase that associates with Fas. Science 268:411–415
Ungefroren H, Kruse ML, Trauzold A, Roeschmann S, Roeder C, Arlt A, Henne-Bruns D, Kalthoff H (2001) FAP-1 in pancreatic cancer cells: functional and mechanistic studies on its inhibitory role in CD95-mediated apoptosis. J Cell Sci 114:2735–2746
Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647–656. doi:10.1038/nrc883nrc883
Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116:205–219
Hill MM, Adrain C, Duriez PJ, Creagh EM, Martin SJ (2004) Analysis of the composition, assembly kinetics and activity of native Apaf-1 apoptosomes. EMBO J 23:2134–2145. doi:10.1038/sjemboj7600210
Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316
Das H, Koizumi T, Sugimoto T, Chakraborty S, Ichimura T, Hasegawa K, Nishimura R (2000) Quantitation of Fas and Fas ligand gene expression in human ovarian, cervical and endometrial carcinomas using real-time quantitative RT-PCR. Br J Cancer 82:1682–1688. doi:10.1054/bjoc.2000.1118
van Haaften-Day C, Russell P, Davies S, King NJ, Tattersall MH (2003) Expression of Fas and FasL in human serous ovarian epithelial tumors. Hum Pathol 34:74–79. doi:10.1053/hupa.2003.7
Ben-Hur H, Gurevich P, Huszar M, Ben-Arie A, Berman V, Tendler Y, Tchanishev R, Zinder O, Mor G, Zaltsman Y, Kohen F, Zusman I (1999) Apoptosis and apoptosis-related proteins in the epithelium of human ovarian tumors: immunohistochemical and morphometric studies. Eur J Gynaecol Oncol 20:249–253
Zusman I, Gurevich P, Gurevich E, Ben-Hur H (2001) The immune system, apoptosis and apoptosis-related proteins in human ovarian tumors (a review). Int J Oncol 18:965–972
Munakata S, Enomoto T, Tsujimoto M, Otsuki Y, Miwa H, Kanno H, Aozasa K (2000) Expressions of Fas ligand and other apoptosis-related genes and their prognostic significance in epithelial ovarian neoplasms. Br J Cancer 82:1446–1452
Meinhold-Heerlein I, Stenner-Liewen F, Liewen H, Kitada S, Krajewska M, Krajewski S, Zapata JM, Monks A, Scudiero DA, Bauknecht T, Reed JC (2001) Expression and potential role of Fas-associated phosphatase-1 in ovarian cancer. Am J Pathol 158:1335–1344. doi:10.1016/S0002-9440(10)64084-9
Marone M, Scambia G, Mozzetti S, Ferrandina G, Iacovella S, De Pasqua A, Benedetti-Panici P, Mancuso S (1998) bcl-2, bax, bcl-XL, and bcl-XS expression in normal and neoplastic ovarian tissues. Clin Cancer Res 4:517–524
Shigemasa K, Katoh O, Shiroyama Y, Mihara S, Mukai K, Nagai N, Ohama K (2002) Increased MCL-1 expression is associated with poor prognosis in ovarian carcinomas. Jpn J Cancer Res 93:542–550
Wehrli BM, Krajewski S, Gascoyne RD, Reed JC, Gilks CB (1998) Immunohistochemical analysis of bcl-2, bax, mcl-1, and bcl-X expression in ovarian surface epithelial tumors. Int J Gynecol Pathol 17:255–260
Chan WY, Cheung KK, Schorge JO, Huang LW, Welch WR, Bell DA, Berkowitz RS, Mok SC (2000) Bcl-2 and p53 protein expression, apoptosis, and p53 mutation in human epithelial ovarian cancers. Am J Pathol 156:409–417. doi:10.1016/S0002-9440(10)64744-X
Miyamoto Y, Hosotani R, Wada M, Lee JU, Koshiba T, Fujimoto K, Tsuji S, Nakajima S, Doi R, Kato M, Shimada Y, Imamura M (1999) Immunohistochemical analysis of Bcl-2, Bax, Bcl-X, and Mcl-1 expression in pancreatic cancers. Oncology 56:73–82
Arts HJ, de Jong S, Hollema H, Ten Hoor KA, de Vries EG, van der Zee AG (2005) Fas and Fas ligand in cyst fluids, serum and tumors of patients with benign and (borderline) malignant ovarian tumors. Int J Oncol 26:379–384
Fauvet R, Dufournet C, Poncelet C, Uzan C, Hugol D, Darai E (2005) Expression of pro-apoptotic (p53, p21, bax, bak and fas) and anti-apoptotic (bcl-2 and bcl-x) proteins in serous versus mucinous borderline ovarian tumours. J Surg Oncol 92:337–343. doi:10.1002/jso.20424
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Parvesh Chaudhry was funded by Indian Council of Medical Research (ICMR) Grant No.: 3/1/JRF/37/MPD/02.
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There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
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Chaudhry, P., Srinivasan, R. & Patel, F.D. Differential expression of Fas family members and Bcl-2 family members in benign versus malignant epithelial ovarian cancer (EOC) in North Indian population. Mol Cell Biochem 368, 119–126 (2012). https://doi.org/10.1007/s11010-012-1350-7
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DOI: https://doi.org/10.1007/s11010-012-1350-7