Skip to main content
Top
Published in: Medical Oncology 1/2012

01-03-2012 | Original Paper

CIP2A is overexpressed in esophageal squamous cell carcinoma

Published in: Medical Oncology | Issue 1/2012

Login to get access

Abstract

A human oncoprotein-designed cancerous inhibitor of PP2A (CIP2A) has been recently identified, which can stabilize c-Myc protein by inhibiting its degradation mediated by protein phosphatase 2A (PP2A) in tumor cells and promote the proliferation of various cancer cells. Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer with poor prognosis worldwide. However, the underlying molecular mechanism of the development of ESCC is still poorly understood. In the present study, the CIP2A expression between normal and malignant esophageal tissues was compared by immunohistochemical analysis; moreover, the mechanisms of CIP2A-mediated tumorigenesis were investigated by evaluating its role in cell proliferation, cell cycle, apoptosis and senescence. We found that the positive staining of CIP2A was found in 36 of 40 (90%) of cancer tissues, whereas only 8 of 40 (20%) normal esophageal mucosa exhibited positive CIP2A staining. The CIP2A is significantly overexpressed in human esophageal tumors when compared with normal tissues (χ2 = 39.6, P < 0.01). On the other hand, the CIP2A expression was not associated with age, gender, tumor burden, or differentiation status. Depletion of CIP2A expression led to impaired clonogenicity and senescence, which is the primary mechanism of CIP2A in oncogenesis. Therefore, CIP2A may be a candidate in diagnosis and therapy of esophageal cancer.
Literature
1.
go back to reference Sablina AA, et al. The tumor suppressor PP2A Aβ regulates the RalA GTPase. Cell. 2007;129:969–82.PubMedCrossRef Sablina AA, et al. The tumor suppressor PP2A Aβ regulates the RalA GTPase. Cell. 2007;129:969–82.PubMedCrossRef
2.
go back to reference Calin GA, et al. Low frequency of alterations of the α (PPP2R1A) and β (PPP2R1B) isoforms of the subunit A of the serine-threonine phosphatase 2A in human neoplasms. Oncogene. 2000;19:1191–5.PubMedCrossRef Calin GA, et al. Low frequency of alterations of the α (PPP2R1A) and β (PPP2R1B) isoforms of the subunit A of the serine-threonine phosphatase 2A in human neoplasms. Oncogene. 2000;19:1191–5.PubMedCrossRef
3.
go back to reference Junttila MR, Westermarck J. Mechanisms of MYC stabilization in human malignancies. Cell Cycle. 2008;7:592–6.PubMedCrossRef Junttila MR, Westermarck J. Mechanisms of MYC stabilization in human malignancies. Cell Cycle. 2008;7:592–6.PubMedCrossRef
4.
go back to reference Yeh E, et al. A signaling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells. Nat Cell Biol. 2004;6:308–18.PubMedCrossRef Yeh E, et al. A signaling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells. Nat Cell Biol. 2004;6:308–18.PubMedCrossRef
6.
go back to reference Li W, Ge Z, Liu C, et al. CIP2A is overexpressed in gastric cancer and its depletion leads to impaired clonogenicity, senescence, or differentiation of tumor cells. Clin Cancer Res. 2008;14:3722–8.PubMedCrossRef Li W, Ge Z, Liu C, et al. CIP2A is overexpressed in gastric cancer and its depletion leads to impaired clonogenicity, senescence, or differentiation of tumor cells. Clin Cancer Res. 2008;14:3722–8.PubMedCrossRef
8.
go back to reference Izzo JG, et al. Cyclin D1 guanine/adenine 870 polymorphism with altered protein expression is associated with genomic instability and aggressive clinical biology of esophageal adenocarcinoma. J Clin Oncol. 2007;25:698–707.PubMedCrossRef Izzo JG, et al. Cyclin D1 guanine/adenine 870 polymorphism with altered protein expression is associated with genomic instability and aggressive clinical biology of esophageal adenocarcinoma. J Clin Oncol. 2007;25:698–707.PubMedCrossRef
9.
go back to reference Bahnassy AA, Zekri AR, Abdallah S, El-Shehaby AM, Sherif GM. Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival. Pathol Int. 2005;55:53–62.PubMedCrossRef Bahnassy AA, Zekri AR, Abdallah S, El-Shehaby AM, Sherif GM. Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival. Pathol Int. 2005;55:53–62.PubMedCrossRef
10.
go back to reference Kanda Y, et al. Analysis of gene amplification and overexpression in human esophageal-carcinoma cell lines. Int J Cancer. 1994;58:291–7.PubMedCrossRef Kanda Y, et al. Analysis of gene amplification and overexpression in human esophageal-carcinoma cell lines. Int J Cancer. 1994;58:291–7.PubMedCrossRef
11.
go back to reference Dimri GP, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA. 1995;92:9363–7.PubMedCrossRef Dimri GP, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA. 1995;92:9363–7.PubMedCrossRef
12.
go back to reference Khanna A, et al. MYC-dependent regulation and prognostic role of CIP2A in gastric cancer. J Natl Cancer Inst. 2009;101:793–805.PubMedCrossRef Khanna A, et al. MYC-dependent regulation and prognostic role of CIP2A in gastric cancer. J Natl Cancer Inst. 2009;101:793–805.PubMedCrossRef
13.
go back to reference Xu D, et al. Switch from Myc/Max to Mad1/Max binding and decrease in histone acetylation at the telomerase reverse transcriptase promoter during differentiation of HL60 cells. Proc Natl Acad Sci USA. 2001;98:3826–31.PubMedCrossRef Xu D, et al. Switch from Myc/Max to Mad1/Max binding and decrease in histone acetylation at the telomerase reverse transcriptase promoter during differentiation of HL60 cells. Proc Natl Acad Sci USA. 2001;98:3826–31.PubMedCrossRef
14.
go back to reference Coˆme C, et al. CIP2A is associated with human breast cancer aggressivity. Clin Cancer Res. 2009;15:5092–100.CrossRef Coˆme C, et al. CIP2A is associated with human breast cancer aggressivity. Clin Cancer Res. 2009;15:5092–100.CrossRef
15.
go back to reference Arroyo JD, Hahn WC. Involvement of PP2A in viral and cellular transformation. Oncogene. 2005;24:7746–55.PubMedCrossRef Arroyo JD, Hahn WC. Involvement of PP2A in viral and cellular transformation. Oncogene. 2005;24:7746–55.PubMedCrossRef
17.
go back to reference Braig M, et al. Oncogene induced senescence as an initial barrier in lymphoma development. Nature. 2005;436:660–5.PubMedCrossRef Braig M, et al. Oncogene induced senescence as an initial barrier in lymphoma development. Nature. 2005;436:660–5.PubMedCrossRef
18.
go back to reference Chen Z, et al. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature. 2005;436:725–30.PubMedCrossRef Chen Z, et al. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature. 2005;436:725–30.PubMedCrossRef
Metadata
Title
CIP2A is overexpressed in esophageal squamous cell carcinoma
Publication date
01-03-2012
Published in
Medical Oncology / Issue 1/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-010-9768-9

Other articles of this Issue 1/2012

Medical Oncology 1/2012 Go to the issue