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Experimental Hematology & Oncology

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Open Access 01-12-2012 | Research

Clinical significance of E2F1 protein expression in non-small cell lung cancer

Authors: Jung-Jyh Hung, Chung-Tsen Hsueh, Kuan-Hua Chen, Wen-Hu Hsu, Yu-Chung Wu

Published in: Experimental Hematology & Oncology | Issue 1/2012

Abstract

Background

The transcription factor E2F1 has been implicated in cell cycle control and DNA damage response. Paradoxically, E2F1 can promote apoptosis and function as tumor suppressor. In non-small cell lung cancer (NSCLC), there are conflicting data for clinical significance of E2F1 expression. In this study, we investigated the protein expression of E2F1 in patients with stage I-III NSCLC, and its correlation with clinical outcome.

Results

56 paired adjacent non-tumor/tumor matched samples were prospectively obtained from patients undergoing surgery for stage I-III NSCLC at Taipei Veterans General Hospital. The protein expression of E2F1 was determined by Western blot analysis. The levels of E2F1 protein were significantly higher in tumor samples than in non-tumor lung specimens (P = 0.008). Overexpression of E2F1 was defined as a more than 2-fold expression in the tumorous sample compared with the corresponding nontumorous one, and was noted in 21 patients (37.5%). There was no significant difference in overall survival (P = 0.44) or probability of freedom from recurrence (P = 0.378) between patients with E2F1 overexpression vs. non-overexpressors. Additionally, there was no significant association between E2F1 overexpression and any clinicopathologic parameter such as histological type, stage, or angiolymphatic invasion of tumor.

Conclusion

E2F1 protein is frequently overexpressed in NSCLC. There is no correlation between E2F1 protein expression and clinical outcome such as survival and freedom from progression.

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Mascaux C, Iannino N, Martin B, Paesmans M, Berghmans T, Dusart M, Haller A, Lothaire P, Meert AP, Noel S, et al.: The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer 2005,92(1):131–139. 10.1038/sj.bjc.6602258PubMedCentralPubMedCrossRef

Steels E, Paesmans M, Berghmans T, Branle F, Lemaitre F, Mascaux C, Meert AP, Vallot F, Lafitte JJ, Sculier JP: Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. Eur Respir J 2001,18(4):705–719. 10.1183/09031936.01.00062201PubMedCrossRef

Zheng Z, Chen T, Li X, Haura E, Sharma A, Bepler G: DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med 2007,356(8):800–808. 10.1056/NEJMoa065411PubMedCrossRef

Stevens C, La Thangue NB: The emerging role of E2F-1 in the DNA damage response and checkpoint control. DNA Repair (Amst) 2004,3(8–9):1071–1079.CrossRef

Ingram L, Munro S, Coutts AS, La Thangue NB: E2F-1 regulation by an unusual DNA damage-responsive DP partner subunit. Cell Death Differ 2011,18(1):122–132. 10.1038/cdd.2010.70PubMedCentralPubMedCrossRef

Van Den Broeck A, Nissou D, Brambilla E, Eymin B, Gazzeri S: Activation of a Tip60/E2F1/ERCC1 network in human lung adenocarcinoma cells exposed to cisplatin. Carcinogenesis 2012,33(2):320–325. 10.1093/carcin/bgr292PubMedCrossRef

Irwin M, Marin MC, Phillips AC, Seelan RS, Smith DI, Liu W, Flores ER, Tsai KY, Jacks T, Vousden KH, et al.: Role for the p53 homologue p73 in E2F-1-induced apoptosis. Nature 2000,407(6804):645–648. 10.1038/35036614PubMedCrossRef

Stiewe T, Putzer BM: Role of the p53-homologue p73 in E2F1-induced apoptosis. Nat Genet 2000,26(4):464–469. 10.1038/82617PubMedCrossRef

Yamasaki L, Jacks T, Bronson R, Goillot E, Harlow E, Dyson NJ: Tumor induction and tissue atrophy in mice lacking E2F-1. Cell 1996,85(4):537–548. 10.1016/S0092-8674(00)81254-4PubMedCrossRef

10.

Field SJ, Tsai FY, Kuo F, Zubiaga AM, Kaelin WG, Livingston DM, Orkin SH, Greenberg ME: E2F-1 functions in mice to promote apoptosis and suppress proliferation. Cell 1996,85(4):549–561. 10.1016/S0092-8674(00)81255-6PubMedCrossRef

11.

Moller MB, Kania PW, Ino Y, Gerdes AM, Nielsen O, Louis DN, Skjodt K, Pedersen NT: Frequent disruption of the RB1 pathway in diffuse large B cell lymphoma: prognostic significance of E2F-1 and p16INK4A. Leukemia 2000,14(5):898–904. 10.1038/sj.leu.2401761PubMedCrossRef

12.

Rabbani F, Richon VM, Orlow I, Lu ML, Drobnjak M, Dudas M, Charytonowicz E, Dalbagni G, Cordon-Cardo C: Prognostic significance of transcription factor E2F-1 in bladder cancer: genotypic and phenotypic characterization. J Natl Cancer Inst 1999,91(10):874–881. 10.1093/jnci/91.10.874PubMedCrossRef

13.

Kwong RA, Nguyen TV, Bova RJ, Kench JG, Cole IE, Musgrove EA, Henshall SM, Sutherland RL: Overexpression of E2F-1 is associated with increased disease-free survival in squamous cell carcinoma of the anterior tongue. Clin Cancer Res 2003,9(10 Pt 1):3705–3711.PubMed

14.

Lee J, Park CK, Park JO, Lim T, Park YS, Lim HY, Lee I, Sohn TS, Noh JH, Heo JS, et al.: Impact of E2F-1 expression on clinical outcome of gastric adenocarcinoma patients with adjuvant chemoradiation therapy. Clin Cancer Res 2008,14(1):82–88. 10.1158/1078-0432.CCR-07-0612PubMedCrossRef

15.

Evangelou K, Kotsinas A, Mariolis-Sapsakos T, Giannopoulos A, Tsantoulis PK, Constantinides C, Troupis TG, Salmas M, Kyroudis A, Kittas C, et al.: E2F-1 overexpression correlates with decreased proliferation and better prognosis in adenocarcinomas of Barrett oesophagus. J Clin Pathol 2008,61(5):601–605. 10.1136/jcp.2007.050963PubMedCrossRef

16.

Saiz AD, Olvera M, Rezk S, Florentine BA, McCourty A, Brynes RK: Immunohistochemical expression of cyclin D1, E2F-1, and Ki-67 in benign and malignant thyroid lesions. J Pathol 2002,198(2):157–162. 10.1002/path.1185PubMedCrossRef

17.

Zhang SY, Liu SC, Al-Saleem LF, Holloran D, Babb J, Guo X, Klein-Szanto AJ: E2F-1: a proliferative marker of breast neoplasia. Cancer Epidemiol Biomarkers Prev 2000,9(4):395–401.PubMed

18.

Volm M, Koomagi R, Rittgen W: Clinical implications of cyclins, cyclin-dependent kinases, RB and E2F1 in squamous-cell lung carcinoma. Int J Cancer 1998,79(3):294–299. 10.1002/(SICI)1097-0215(19980619)79:3<294::AID-IJC15>3.0.CO;2-8PubMedCrossRef

19.

Huang CL, Liu D, Nakano J, Yokomise H, Ueno M, Kadota K, Wada H: E2F1 overexpression correlates with thymidylate synthase and survivin gene expressions and tumor proliferation in non small-cell lung cancer. Clin Cancer Res 2007,13(23):6938–6946. 10.1158/1078-0432.CCR-07-1539PubMedCrossRef

20.

Gorgoulis VG, Zacharatos P, Mariatos G, Kotsinas A, Bouda M, Kletsas D, Asimacopoulos PJ, Agnantis N, Kittas C, Papavassiliou AG: Transcription factor E2F-1 acts as a growth-promoting factor and is associated with adverse prognosis in non-small cell lung carcinomas. J Pathol 2002,198(2):142–156. 10.1002/path.1121PubMedCrossRef

21.

Yamazaki K, Hasegawa M, Ohoka I, Hanami K, Asoh A, Nagao T, Sugano I, Ishida Y: Increased E2F-1 expression via tumour cell proliferation and decreased apoptosis are correlated with adverse prognosis in patients with squamous cell carcinoma of the oesophagus. J Clin Pathol 2005,58(9):904–910. 10.1136/jcp.2004.023127PubMedCentralPubMedCrossRef

22.

Kwon MJ, Nam ES, Cho SJ, Park HR, Shin HS, Park JH, Park CH, Lee WJ: E2F1 expression predicts outcome in Korean women who undergo surgery for breast carcinoma. Ann Surg Oncol 2010,17(2):564–571. 10.1245/s10434-009-0767-zPubMedCrossRef

23.

Cho EC, Zheng S, Munro S, Liu G, Carr SM, Moehlenbrink J, Lu YC, Stimson L, Khan O, Konietzny R, et al.: Arginine methylation controls growth regulation by E2F-1. EMBO J 2012,31(7):1785–1797. 10.1038/emboj.2012.17PubMedCentralPubMedCrossRef

24.

Hallett RM, Hassell JA: E2F1 and KIAA0191 expression predicts breast cancer patient survival. BMC Res Notes 2011, 4: 95. 10.1186/1756-0500-4-95PubMedCentralPubMedCrossRef

25.

Hsueh CT, Wu YC, Schwartz GK: UCN-01 suppresses E2F-1 mediated by ubiquitin-proteasome-dependent degradation. Clin Cancer Res 2001,7(3):669–674.PubMed

26.

Novotny GW, Sonne SB, Nielsen JE, Jonstrup SP, Hansen MA, Skakkebaek NE, Rajpert-De Meyts E, Kjems J, Leffers H: Translational repression of E2F1 mRNA in carcinoma in situ and normal testis correlates with expression of the miR-17–92 cluster. Cell Death Differ 2007,14(4):879–882. 10.1038/sj.cdd.4402090PubMedCrossRef

27.

Yang G, Zhang R, Chen X, Mu Y, Ai J, Shi C, Liu Y, Sun L, Rainov NG, Li H, et al.: MiR-106a inhibits glioma cell growth by targeting E2F1 independent of p53 status. J Mol Med (Berl) 2011,89(10):1037–1050. 10.1007/s00109-011-0775-xCrossRef

28.

Wang HW, Hsueh CT, Lin CF, Chou TY, Hsu WH, Wang LS, Wu YC: Clinical implications of microsomal prostaglandin e synthase-1 overexpression in human non-small-cell lung cancer. Ann Surg Oncol 2006,13(9):1224–1234. 10.1245/s10434-006-9001-4PubMedCrossRef

Title: Clinical significance of E2F1 protein expression in non-small cell lung cancer
Authors: Jung-Jyh Hung
Chung-Tsen Hsueh
Kuan-Hua Chen
Wen-Hu Hsu
Yu-Chung Wu
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Experimental Hematology & Oncology / Issue 1/2012
Electronic ISSN: 2162-3619
DOI: https://doi.org/10.1186/2162-3619-1-18

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Abstract

Background

Results

Conclusion

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