Endogenous BTG2 expression stimulates migration of bladder cancer cells and correlates with poor clinical prognosis for bladder cancer patients

被引：37

作者：

Wagener, N. ^{[1
]}

Bulkescher, J. ^{[2
]}

Macher-Goeppinger, S. ^{[3
]}

Karapanagiotou-Schenkel, I. ^{[4
]}

Hatiboglu, G. ^{[1
]}

Abdel-Rahim, M. ^{[5
]}

Abol-Enein, H. ^{[5
]}

Ghoneim, M. A. ^{[5
]}

Bastian, P. J. ^{[6
,7
]}

Mueller, S. C. ^{[6
]}

Haferkamp, A. ^{[8
]}

Hohenfellner, M. ^{[1
]}

Hoppe-Seyler, F. ^{[2
]}

Hoppe-Seyler, K. ^{[2
]}

机构：

[1] Heidelberg Univ, Dept Urol, D-69120 Heidelberg, Germany

[2] German Canc Res Ctr, D-69120 Heidelberg, Germany

[3] Heidelberg Univ, Inst Pathol, D-69120 Heidelberg, Germany

[4] German Canc Res Ctr, NCT Clin Trial Ctr, D-69120 Heidelberg, Germany

[5] Univ Mansoura, Urol & Nephrol Ctr, Dept Urol, Mansoura 35516, Egypt

[6] Univ Bonn, Dept Urol, D-53105 Bonn, Germany

[7] Univ Munich, Dept Urol, D-81377 Munich, Germany

[8] Goethe Univ Frankfurt, Dept Urol, D-60590 Frankfurt, Germany

来源：

BRITISH JOURNAL OF CANCER | 2013年 / 108卷 / 04期

关键词：

bladder cancer; BTG2; cell migration; tumour suppressor; TUMOR PROGRESSION; CYCLE REGULATOR; BREAST-CANCER; MODEL; OVEREXPRESSION; SUPPRESSION; INHIBITION; CARCINOMA; SURVIVAL; FREQUENT;

D O I：

10.1038/bjc.2012.573

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: The B-cell translocation gene 2 (BTG2) is considered to act as a tumour-suppressor gene because of its antiproliferative and antimigratory activities. Higher levels of BTG2 expression in tumour cells have been linked to a better clinical outcome for several cancer entities. Here, we investigated the expression and function of BTG2 in bladder cancer. Methods: The expression of BTG2 in bladder cancer cells was silenced by RNA interference. Cell motility was investigated by wound healing and Boyden chamber assays. The protein expression of BTG2 in bladder cancer was studied by immunohistochemistry. Results: We observed that targeted suppression of BTG2 by RNA interference did not result in growth stimulation but led to a substantial inhibition of bladder cancer cell motility. Tissue microarray analyses of bladder cancer cystectomy specimens revealed that higher BTG2 expression levels within the tumours correlated strongly with a decreased cancer-specific survival for bladder cancer patients. Conclusion: These results indicate that endogenous BTG2 expression contributes to the migratory potential of bladder cancer cells. Moreover, high levels of BTG2 in bladder cancers are linked to decreased cancer-specific survival. These findings question the conception that BTG2 generally acts as a tumour suppressor and typically represents a favourable clinical marker for cancer patients.

引用

页码：973 / 982

页数：10

共 39 条

[1] A systematic search for downstream mediators of tumor suppressor function of p53 reveals a major role of BTG2 in suppression of Ras-induced transformation [J].

Boiko, AD ;

Porteous, S ;

Razorenova, OV ;

Krivokrysenko, VI ;

Williams, BR ;

Gudkov, AV .

GENES & DEVELOPMENT, 2006, 20 (02) :236-252

[2]

CAIRNS P, 1991, ONCOGENE, V6, P2305

[3] Tumor Progression and Oncogene Addiction in a PDGF-B-Induced Model of Gliomagenesis [J].

Calzolari, Filippo ;

Appolloni, Irene ;

Tutucci, Evelina ;

Caviglia, Sara ;

Terrile, Marta ;

Corte, Giorgio ;

Malatesta, Paolo .

NEOPLASIA, 2008, 10 (12) :1373-U51

[4] Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas [J].

Cappellen, D ;

De Oliveira, C ;

Ricol, D ;

de Medina, SGD ;

Bourdin, J ;

Sastre-Garau, X ;

Chopin, D ;

Thiery, JP ;

Radvanyi, F .

NATURE GENETICS, 1999, 23 (01) :18-20

[5] High-throughput SNP-based authentication of human cell lines [J].

Castro, Felipe ;

Dirks, Wilhelm G. ;

Faehnrich, Silke ;

Hotz-Wagenblatt, Agnes ;

Pawlita, Michael ;

Schmitt, Markus .

INTERNATIONAL JOURNAL OF CANCER, 2013, 132 (02) :308-314

[6]

Chen Hong-Chen, 2004, V294, P15

[7] Suppression of mammary carcinoma cell growth by retinoic acid:: the cell cycle control gene Btg2 is a direct target for retinoic acid receptor signaling [J].

Donato, Leslie J. ;

Suh, Jean H. ;

Noy, Noa .

CANCER RESEARCH, 2007, 67 (02) :609-615

[8]

Duriez Cyril, 2004, Bull Cancer, V91, pE242

[9] BTG2TIS21/PC3 induces neuronal differentiation and prevents apoptosis of terminally differentiated PC12 cells [J].

el-Ghissassi, F ;

Valsesia-Wittmann, S ;

Falette, N ;

Duriez, C ;

Walden, PD ;

Puisieux, A .

ONCOGENE, 2002, 21 (44) :6772-6778

[10] Evasion of a single-step, chemotherapy-induced senescence in breast cancer cells: Implications for treatment response [J].

Elmore, LW ;

Di, X ;

Dumur, C ;

Holt, SE ;

Gewirtz, DA .

CLINICAL CANCER RESEARCH, 2005, 11 (07) :2637-2643

← 1 2 3 4 →