FEZ1/LZTS1 is down-regulated in high-grade bladder cancer, and its restoration suppresses tumorigenicity in transitional cell carcinoma cells.
FEZ1/LZTS1 is a tumor suppressor gene that maps to chromosome 8p22, a chromosomal region frequently deleted in many human malignancies, including transitional cell carcinoma (TCC) of the urinary bladder. FEZ1/LZTS1 alterations have been reported in esophageal, breast, prostate, and gastric carcinomas. Fez1 expression was studied in five TCC-derived cancer cell lines by Western blot analysis and in 60 primary TCCs of the urinary bladder by immunohistochemistry. Fez1 protein was absent or reduced in four of five cell lines and in 37 of 60 primary TCC examined. We also restored Fez1 protein expression in human SW780 TCC-derived cells lacking endogenous Fez1 protein to study the effects of Fez1 expression on cell proliferation, cell kinetics, and tumorigenicity in BALB/c nude mice. In vitro transduction of SW780 Fez1-negative cell, with Ad-FEZ1, inhibited cell growth, altered cell cycle progression, and suppressed subcutaneous tumor growth in nude mice. These results suggest that FEZ1/LZTS1 gene plays a role in the development of TCC of the urinary bladder by acting as a bona fide tumor suppressor gene both in vitro and in vivo.
Vecchione
Andrea
A
Department of Urology, Kimmel Cancer Center,Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Ishii
Hideshi
H
Baldassarre
Gustavo
G
Bassi
Pierfrancesco
P
Trapasso
Francesco
F
Alder
Hansjuerg
H
Pagano
Francesco
F
Gomella
Leonard G
LG
Croce
Carlo M
CM
Baffa
Raffaele
R
D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015197:Carcinogenicity Tests; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D018844:Cyclin-Dependent Kinases; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis / Q000502:physiology; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C528597:FEZ1 protein, human; C118711:LZTS1 protein, human; C574993:Lzts1 protein, mouse; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase