Skip to main content
Top
Published in: World Journal of Surgery 1/2012

Open Access 01-01-2012

Cytoplasmic Forkhead Box M1 (FoxM1) in Esophageal Squamous Cell Carcinoma Significantly Correlates with Pathological Disease Stage

Authors: Marco K. C. Hui, Kwok Wah Chan, John M. Luk, Nikki P. Lee, Yvonne Chung, Leo C. M. Cheung, Gopesh Srivastava, Sai Wah Tsao, Johnny C. Tang, Simon Law

Published in: World Journal of Surgery | Issue 1/2012

Login to get access

Abstract

Esophageal cancer is a deadly cancer with esophageal squamous cell carcinoma (ESCC) as the major type. Until now there has been a lack of reliable prognostic markers for this malignancy. This study aims to investigate the clinical correlation between Forkhead box M1 (FoxM1) and patients’ parameters in ESCC.

Methods

Immunohistochemistry was performed to investigate the expression and localization of FoxM1 in 64 ESCC tissues and 10 nontumor esophageal tissues randomly selected from 64 patients before these data were used for clinical correlations.

Results

Cytoplasmic and nuclear expressions of FoxM1 were found in 63 and 16 of the 64 ESCC tissues, respectively. Low cytoplasmic expression of FoxM1 was correlated with early pathological stage in ESCC (P = 0.018), while patients with nuclear FoxM1 were younger in age than those without nuclear expression (P < 0.001). Upregulation of FoxM1 mRNA was found in five ESCC cell lines (HKESC-1, HKESC-2, HKESC-3, HKESC-4, and SLMT-1) when compared to non-neoplastic esophageal squamous cell line NE-1 using quantitative polymerase chain reaction (qPCR). Except for HKESC-3, all studied ESCC cell lines demonstrated a high expression of FoxM1 protein using immunoblot. A high mRNA level of FoxM1 was observed in all of the ESCC tissues examined when compared to their adjacent nontumor tissues using qPCR.

Conclusion

Cytoplasmic FoxM1 was correlated with pathological stage and might be a biomarker for advanced ESCC.
Literature
1.
go back to reference Laoukili J, Stahl M, Medema RH (2007) FoxM1: at the crossroads of ageing and cancer. Biochim Biophys Acta 1775:92–102PubMed Laoukili J, Stahl M, Medema RH (2007) FoxM1: at the crossroads of ageing and cancer. Biochim Biophys Acta 1775:92–102PubMed
2.
go back to reference Yu J, Deshmukh H, Payton JE et al (2011) Array-based comparative genomic hybridization identifies CDK4 and FOXM1 alterations as independent predictors of survival in malignant peripheral nerve sheath tumor. Clin Cancer Res 17:1924–1934PubMedCrossRef Yu J, Deshmukh H, Payton JE et al (2011) Array-based comparative genomic hybridization identifies CDK4 and FOXM1 alterations as independent predictors of survival in malignant peripheral nerve sheath tumor. Clin Cancer Res 17:1924–1934PubMedCrossRef
3.
go back to reference Myatt SS, Lam EW (2007) The emerging roles of forkhead box (Fox) proteins in cancer. Nat Rev Cancer 7:847–859PubMedCrossRef Myatt SS, Lam EW (2007) The emerging roles of forkhead box (Fox) proteins in cancer. Nat Rev Cancer 7:847–859PubMedCrossRef
4.
go back to reference Wierstra I, Alves J (2007) FOXM1, a typical proliferation-associated transcription factor. Biol Chem 388:1257–1274PubMedCrossRef Wierstra I, Alves J (2007) FOXM1, a typical proliferation-associated transcription factor. Biol Chem 388:1257–1274PubMedCrossRef
5.
go back to reference Kalin TV, Wang IC, Ackerson TJ et al (2006) Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice. Cancer Res 66:1712–1720PubMedCrossRef Kalin TV, Wang IC, Ackerson TJ et al (2006) Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice. Cancer Res 66:1712–1720PubMedCrossRef
6.
go back to reference Yoshida Y, Wang IC, Yoder HM et al (2007) The forkhead box M1 transcription factor contributes to the development and growth of mouse colorectal cancer. Gastroenterology 132:1420–1431PubMedCrossRef Yoshida Y, Wang IC, Yoder HM et al (2007) The forkhead box M1 transcription factor contributes to the development and growth of mouse colorectal cancer. Gastroenterology 132:1420–1431PubMedCrossRef
7.
go back to reference Zhao YY, Gao XP, Zhao YD et al (2006) Endothelial cell-restricted disruption of FoxM1 impairs endothelial repair following LPS-induced vascular injury. J Clin Invest 116:2333–2343PubMedCrossRef Zhao YY, Gao XP, Zhao YD et al (2006) Endothelial cell-restricted disruption of FoxM1 impairs endothelial repair following LPS-induced vascular injury. J Clin Invest 116:2333–2343PubMedCrossRef
8.
go back to reference Tan Y, Yoshida Y, Hughes DE et al (2006) Increased expression of hepatocyte nuclear factor 6 stimulates hepatocyte proliferation during mouse liver regeneration. Gastroenterology 130:1283–1300PubMedCrossRef Tan Y, Yoshida Y, Hughes DE et al (2006) Increased expression of hepatocyte nuclear factor 6 stimulates hepatocyte proliferation during mouse liver regeneration. Gastroenterology 130:1283–1300PubMedCrossRef
9.
go back to reference Teh MT, Wong ST, Neill GW et al (2002) FOXM1 is a downstream target of Gli1 in basal cell carcinomas. Cancer Res 62:4773–4780PubMed Teh MT, Wong ST, Neill GW et al (2002) FOXM1 is a downstream target of Gli1 in basal cell carcinomas. Cancer Res 62:4773–4780PubMed
10.
go back to reference Liu M, Dai B, Kang SH et al (2006) FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells. Cancer Res 66:3593–3602PubMedCrossRef Liu M, Dai B, Kang SH et al (2006) FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells. Cancer Res 66:3593–3602PubMedCrossRef
11.
go back to reference Kim IM, Ackerson T, Ramakrishna S et al (2006) The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. Cancer Res 66:2153–2161PubMedCrossRef Kim IM, Ackerson T, Ramakrishna S et al (2006) The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. Cancer Res 66:2153–2161PubMedCrossRef
12.
go back to reference Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752PubMedCrossRef Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752PubMedCrossRef
13.
go back to reference Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869–10874PubMedCrossRef Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869–10874PubMedCrossRef
14.
go back to reference Kalinichenko VV, Major ML, Wang X et al (2004) Foxm1b transcription factor is essential for development of hepatocellular carcinomas and is negatively regulated by the p19ARF tumor suppressor. Genes Dev 18:830–850PubMedCrossRef Kalinichenko VV, Major ML, Wang X et al (2004) Foxm1b transcription factor is essential for development of hepatocellular carcinomas and is negatively regulated by the p19ARF tumor suppressor. Genes Dev 18:830–850PubMedCrossRef
15.
16.
go back to reference Cheung LC, Tang JC, Lee PY et al (2007) Establishment and characterization of a new xenograft-derived human esophageal squamous cell carcinoma cell line HKESC-4 of Chinese origin. Cancer Genet Cytogenet 178:17–25PubMedCrossRef Cheung LC, Tang JC, Lee PY et al (2007) Establishment and characterization of a new xenograft-derived human esophageal squamous cell carcinoma cell line HKESC-4 of Chinese origin. Cancer Genet Cytogenet 178:17–25PubMedCrossRef
17.
go back to reference Hu Y, Lam KY, Wan TS et al (2000) Establishment and characterization of HKESC-1, a new cancer cell line from human esophageal squamous cell carcinoma. Cancer Genet Cytogenet 118:112–120PubMedCrossRef Hu Y, Lam KY, Wan TS et al (2000) Establishment and characterization of HKESC-1, a new cancer cell line from human esophageal squamous cell carcinoma. Cancer Genet Cytogenet 118:112–120PubMedCrossRef
18.
go back to reference Hu YC, Lam KY, Law SY et al (2002) Establishment, characterization, karyotyping, and comparative genomic hybridization analysis of HKESC-2 and HKESC-3: two newly established human esophageal squamous cell carcinoma cell lines. Cancer Genet Cytogenet 135:120–127PubMedCrossRef Hu YC, Lam KY, Law SY et al (2002) Establishment, characterization, karyotyping, and comparative genomic hybridization analysis of HKESC-2 and HKESC-3: two newly established human esophageal squamous cell carcinoma cell lines. Cancer Genet Cytogenet 135:120–127PubMedCrossRef
19.
go back to reference Tang JC, Wan TS, Wong N et al (2001) Establishment and characterization of a new xenograft-derived human esophageal squamous cell carcinoma cell line SLMT-1 of Chinese origin. Cancer Genet Cytogenet 124:36–41PubMedCrossRef Tang JC, Wan TS, Wong N et al (2001) Establishment and characterization of a new xenograft-derived human esophageal squamous cell carcinoma cell line SLMT-1 of Chinese origin. Cancer Genet Cytogenet 124:36–41PubMedCrossRef
20.
go back to reference Zhang H, Jin Y, Chen X et al (2006) Cytogenetic aberrations in immortalization of esophageal epithelial cells. Cancer Genet Cytogenet 165:25–35PubMedCrossRef Zhang H, Jin Y, Chen X et al (2006) Cytogenetic aberrations in immortalization of esophageal epithelial cells. Cancer Genet Cytogenet 165:25–35PubMedCrossRef
21.
go back to reference Lee NP, Leung KW, Cheung N et al (2008) Comparative proteomic analysis of mouse livers from embryo to adult reveals an association with progression of hepatocellular carcinoma. Proteomics 8:2136–2149PubMedCrossRef Lee NP, Leung KW, Cheung N et al (2008) Comparative proteomic analysis of mouse livers from embryo to adult reveals an association with progression of hepatocellular carcinoma. Proteomics 8:2136–2149PubMedCrossRef
22.
go back to reference Lee NP, Tsang FH, Shek FH et al (2010) Prognostic significance and therapeutic potential of eukaryotic translation initiation factor 5A (eIF5A) in hepatocellular carcinoma. Int J Cancer 127:968–976PubMedCrossRef Lee NP, Tsang FH, Shek FH et al (2010) Prognostic significance and therapeutic potential of eukaryotic translation initiation factor 5A (eIF5A) in hepatocellular carcinoma. Int J Cancer 127:968–976PubMedCrossRef
23.
go back to reference Lee NP, Chen L, Lin MC et al (2009) Proteomic expression signature distinguishes cancerous and nonmalignant tissues in hepatocellular carcinoma. J Proteome Res 8:1293–1303PubMedCrossRef Lee NP, Chen L, Lin MC et al (2009) Proteomic expression signature distinguishes cancerous and nonmalignant tissues in hepatocellular carcinoma. J Proteome Res 8:1293–1303PubMedCrossRef
24.
go back to reference Lee NP, Leung KW, Wo JY et al (2006) Blockage of testicular connexins induced apoptosis in rat seminiferous epithelium. Apoptosis 11:1215–1229PubMedCrossRef Lee NP, Leung KW, Wo JY et al (2006) Blockage of testicular connexins induced apoptosis in rat seminiferous epithelium. Apoptosis 11:1215–1229PubMedCrossRef
25.
go back to reference Lee NP, Tong MK, Leung PP et al (2006) Kidney claudin-19: localization in distal tubules and collecting ducts and dysregulation in polycystic renal disease. FEBS Lett 580:923–931PubMedCrossRef Lee NP, Tong MK, Leung PP et al (2006) Kidney claudin-19: localization in distal tubules and collecting ducts and dysregulation in polycystic renal disease. FEBS Lett 580:923–931PubMedCrossRef
26.
go back to reference Chung Y, Lam AK, Luk JM et al (2007) Altered E-cadherin expression and p120 catenin localization in esophageal squamous cell carcinoma. Ann Surg Oncol 14:3260–3267PubMedCrossRef Chung Y, Lam AK, Luk JM et al (2007) Altered E-cadherin expression and p120 catenin localization in esophageal squamous cell carcinoma. Ann Surg Oncol 14:3260–3267PubMedCrossRef
27.
go back to reference Chan DW, Yu SY, Chiu PM et al (2008) Over-expression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesis. J Pathol 215:245–252PubMedCrossRef Chan DW, Yu SY, Chiu PM et al (2008) Over-expression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesis. J Pathol 215:245–252PubMedCrossRef
28.
go back to reference Ly DH, Lockhart DJ, Lerner RA et al (2000) Mitotic misregulation and human aging. Science 287:2486–2492PubMedCrossRef Ly DH, Lockhart DJ, Lerner RA et al (2000) Mitotic misregulation and human aging. Science 287:2486–2492PubMedCrossRef
29.
go back to reference Kalinichenko VV, Gusarova GA, Tan Y et al (2003) Ubiquitous expression of the forkhead box M1B transgene accelerates proliferation of distinct pulmonary cell types following lung injury. J Biol Chem 278:37888–37894PubMedCrossRef Kalinichenko VV, Gusarova GA, Tan Y et al (2003) Ubiquitous expression of the forkhead box M1B transgene accelerates proliferation of distinct pulmonary cell types following lung injury. J Biol Chem 278:37888–37894PubMedCrossRef
30.
go back to reference Laoukili J, Kooistra MR, Bras A et al (2005) FoxM1 is required for execution of the mitotic programme and chromosome stability. Nat Cell Biol 7:126–136PubMedCrossRef Laoukili J, Kooistra MR, Bras A et al (2005) FoxM1 is required for execution of the mitotic programme and chromosome stability. Nat Cell Biol 7:126–136PubMedCrossRef
31.
go back to reference Maity P, Biswas K, Roy S et al (2003) Smoking and the pathogenesis of gastroduodenal ulcer–recent mechanistic update. Mol Cell Biochem 253:329–338PubMedCrossRef Maity P, Biswas K, Roy S et al (2003) Smoking and the pathogenesis of gastroduodenal ulcer–recent mechanistic update. Mol Cell Biochem 253:329–338PubMedCrossRef
32.
go back to reference Wang SL, Milles M, Wu-Wang CY et al (1992) Effect of cigarette smoking on salivary epidermal growth factor (EGF) and EGF receptor in human buccal mucosa. Toxicology 75:145–157PubMedCrossRef Wang SL, Milles M, Wu-Wang CY et al (1992) Effect of cigarette smoking on salivary epidermal growth factor (EGF) and EGF receptor in human buccal mucosa. Toxicology 75:145–157PubMedCrossRef
33.
go back to reference Balbis A, Posner BI (2010) Compartmentalization of EGFR in cellular membranes: role of membrane rafts. J Cell Biochem 109:1103–1108PubMed Balbis A, Posner BI (2010) Compartmentalization of EGFR in cellular membranes: role of membrane rafts. J Cell Biochem 109:1103–1108PubMed
34.
go back to reference Ma RY, Tong TH, Cheung AM et al (2005) Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1c. J Cell Sci 118:795–806PubMedCrossRef Ma RY, Tong TH, Cheung AM et al (2005) Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1c. J Cell Sci 118:795–806PubMedCrossRef
Metadata
Title
Cytoplasmic Forkhead Box M1 (FoxM1) in Esophageal Squamous Cell Carcinoma Significantly Correlates with Pathological Disease Stage
Authors
Marco K. C. Hui
Kwok Wah Chan
John M. Luk
Nikki P. Lee
Yvonne Chung
Leo C. M. Cheung
Gopesh Srivastava
Sai Wah Tsao
Johnny C. Tang
Simon Law
Publication date
01-01-2012
Publisher
Springer-Verlag
Published in
World Journal of Surgery / Issue 1/2012
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-011-1302-5

Other articles of this Issue 1/2012

World Journal of Surgery 1/2012 Go to the issue