CIP2A is overexpressed in esophageal squamous cell carcinoma

被引:67
作者
Qu, Wei [1 ,2 ]
Li, Wenjuan [2 ]
Wei, Ling [3 ]
Xing, Ligang [1 ]
Wang, Xingwu [3 ]
Yu, Jinming [1 ]
机构
[1] Shandong Canc Hosp & Inst, Key Lab Radiat Oncol Shandong Prov, Dept Radiat Oncol, Jinan 250117, Shandong, Peoples R China
[2] Shandong Univ, Sch Med, Dept Microbiol & Immunol, Key Lab Expt Teratol Chinese,Minist Educ, Jinan 250012, Shandong, Peoples R China
[3] Shandong Canc Hosp & Inst, Canc Res Ctr, Key Lab Radiat Oncol Shandong Prov, Jinan 250117, Shandong, Peoples R China
关键词
Esophageal squamous cell carcinoma (ESCC); Cancerous inhibitor of PP2A (CIP2A); siRNA; Senescence; HUMAN MALIGNANCIES; GASTRIC-CANCER; SENESCENCE; PP2A; DIFFERENTIATION; TRANSFORMATION; SUPPRESSION;
D O I
10.1007/s12032-010-9768-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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 (chi(2) = 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.
引用
收藏
页码:113 / 118
页数:6
相关论文
共 18 条
[1]
Chemoradiotheraphy of esophageal cancer [J].
Albertsson, M .
ACTA ONCOLOGICA, 2002, 41 (02) :118-123
[2]
Involvement of PP2A in viral and cellular transformation [J].
Arroyo, JD ;
Hahn, WC .
ONCOGENE, 2005, 24 (52) :7746-7755
[3]
Human papillomavirus infection in Egyptian esophageal carcinoma:: Correlation with p53, p21waf, mdm2, C-erbB2 and impact on survival [J].
Bahnassy, AA ;
Zekri, ARN ;
Abdallah, S ;
El-Shehaby, AMR ;
Sherif, GM .
PATHOLOGY INTERNATIONAL, 2005, 55 (02) :53-62
[4]
Oncogene-induced senescence as an initial barrier in lymphoma development [J].
Braig, M ;
Lee, S ;
Loddenkemper, C ;
Rudolph, C ;
Peters, AHFM ;
Schlegelberger, B ;
Stein, H ;
Dörken, B ;
Jenuwein, T ;
Schmitt, CA .
NATURE, 2005, 436 (7051) :660-665
[5]
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 [J].
Calin, GA ;
di Iasio, MG ;
Caprini, E ;
Vorechovsky, I ;
Natali, PG ;
Sozzi, G ;
Croce, CM ;
Barbanti-Brodano, G ;
Russo, G ;
Negrini, M .
ONCOGENE, 2000, 19 (09) :1191-1195
[6]
Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis [J].
Chen, ZB ;
Trotman, LC ;
Shaffer, D ;
Lin, HK ;
Dotan, ZA ;
Niki, M ;
Koutcher, JA ;
Scher, HI ;
Ludwig, T ;
Gerald, W ;
Cordon-Cardo, C ;
Pandolfi, PP .
NATURE, 2005, 436 (7051) :725-730
[7]
CIP2A Is Associated with Human Breast Cancer Aggressivity [J].
Come, Christophe ;
Laine, Anni ;
Chanrion, Maia ;
Edgren, Henrik ;
Mattila, Elina ;
Liu, Xiaoling ;
Jonkers, Jos ;
Ivaska, Johanna ;
Isola, Jorma ;
Darbon, Jean-Marie ;
Kallioniemi, Olli ;
Thezenas, Simon ;
Westermarck, Jukka .
CLINICAL CANCER RESEARCH, 2009, 15 (16) :5092-5100
[8]
A BIOMARKER THAT IDENTIFIES SENESCENT HUMAN-CELLS IN CULTURE AND IN AGING SKIN IN-VIVO [J].
DIMRI, GP ;
LEE, XH ;
BASILE, G ;
ACOSTA, M ;
SCOTT, C ;
ROSKELLEY, C ;
MEDRANO, EE ;
LINSKENS, M ;
RUBELJ, I ;
PEREIRASMITH, O ;
PEACOCKE, M ;
CAMPISI, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (20) :9363-9367
[9]
Cyclin D1 guanine/adenine 870 polymorphism with altered protein expression is associated with genomic instability and aggressive clinical biology of esophageal adenocarcinoma [J].
Izzo, Julie G. ;
Wu, Tsung-Teh ;
Wu, Xifeng ;
Ensor, Joe ;
Luthra, Rajyalakshmi ;
Pan, Jennifer ;
Correa, Arlene ;
Swisher, Stephen G. ;
Chao, Clifford K. S. ;
Hittelman, Walter N. ;
Ajani, Jaffer A. .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (06) :698-707
[10]
Mechanisms of MYC stabilization in human malignancies [J].
Junttila, Melissa R. ;
Westermarck, Jukka .
CELL CYCLE, 2008, 7 (05) :592-596