FEZ1/LZTS1 is down-regulated in high-grade bladder cancer, and its restoration suppresses tumorigenicity in transitional cell carcinoma cells

Andrea Vecchione, Hideshi Ishii, Gustavo Baldassarre, Pierfrancesco Bassi, Francesco Trapasso, Hansjuerg Alder, Francesco Pagano, Leonard G. Gomella, Carlo M. Croce, Raffaele Baffa

Research output: Contribution to journalArticlepeer-review

Abstract

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 Fezl-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 bonafide tumor suppressor gene both in vitro and in vivo.

Original languageEnglish
Pages (from-to)1345-1352
Number of pages8
JournalAmerican Journal of Pathology
Volume160
Issue number4
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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