MTDH/AEG-1 contributes to central features of the neoplastic phenotype in bladder cancer.
OBJECTIVE
Carcinoma of the bladder is the fifth most common cancer whose incidence continues to rise. MTDH/AEG-1 is associated with the initiation and progression of many cancers including breast, hepatocellular, ovarian, and colorectal carcinomas. However, the expression and functional importance of MTDH/AEG-1 in bladder cancer remains unknown. The present study was aimed at exploring the functional role of MTDH/AEG-1 in selected bladder cancer cell lines.


METHODS
The relative expression of MTDH/AEG-1 was assessed by real-time quantitative reverse transcription-polymerase chain reaction in several human bladder cancer cell lines as well as cancerous and benign bladder tissues. Then, expression of MTDH/AEG-1 in RT112 and 647V bladder cancer cell lines was knocked down by an RNA interference strategy. Cell viability and apoptosis were determined after treatment with specific interfering RNA. Potential effects of MTDG/AEG-1 specific interfering RNA on the cell cycle were investigated by flow cytometry. We also performed anchorage-independent growth and wound-healing assays to study MTDH/AEG-1 function.


RESULTS
Down-regulation of MTDH/AEG-1 did not significantly affect the cell cycle distribution but rather reduced cell viability via apoptosis, as evidenced by increased annexin V staining and caspase 3/7 activities as well as mitochondrial potential disruption. Of note, serum starvation did not exacerbate the effects of MTDH/AEG-1 knockdown. Furthermore, MTDH/AEG-1 down-regulation significantly decreased anchorage-independent growth and migration of bladder carcinoma cells.


CONCLUSIONS
Overexpression of MTDH/AEG-1 contributes to the neoplastic phenotype of bladder cancer cells by promoting survival, clonogenicity, and migration.
Department of Urology, Heinrich Heine University, Düsseldorf, Germany; Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Mahnaz
M
Nikpour
Department of Genetics, School of Basic Sciences, Shahrekord University, Shahrekord, Iran; Research Institute of Biotechnology, School of Basic Sciences, Shahrekord University, Shahrekord, Iran.
Modjtaba
M
Emadi-Baygi
Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Heinrich Heine University, Düsseldorf, Germany.
Ute
U
Fischer
Department of Urology, Heinrich Heine University, Düsseldorf, Germany.
Günter
G
Niegisch
Department of Urology, Heinrich Heine University, Düsseldorf, Germany.
Wolfgang A
WA
Schulz
Pediatric Inherited Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address: pnikpour@med.mui.ac.ir.
Parvaneh
P
Nikpour
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010641:Phenotype; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins; D001743:Urinary Bladder / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*; D014945:Wound Healing
D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7
Anchorage-independent growth; Bladder cancer; Cell survival; MTDH/AEG-1