title: Aberrant FHIT expression is linked to bladder carcinogenesis and apoptosis.
abstract: The fragile histidine triad gene (FHIT) functions as tumor suppressor in many epithelial cell types. Although the exact mechanisms remain unclear, it is apparent that in its absence, cell cycle homeostasis is often perturbed resulting in the development of soft tissue tumors. Here, we investigated the role of FHIT expression in bladder carcinogenesis and progression using immunohistochemistry. Bladder carcinoma tissue and the 5637 cell line were also studied for FHIT expression by RT-PCR and Western blotting, respectively. FHIT was found to be expressed in carcinoma and adjacent normal tissues at both mRNA and protein levels, but the 17 kDa FHIT was lower in tumors (P<0.05), this being confirmed immunohistochemically. There was a negative correlation between FHIT expression and histological grade of bladder transitional cell carcinoma (P<0.05), but no clear relationship with clinical stage or relapse (P>0.05). Overexpression of FHIT could induce apoptosis in bladder carcinoma 5637 cells, which could be enhanced by adding adriamycin (ADR). These findings suggest important roles of FHIT in bladder cancer development and provide support for the feasibility of FHIT-based gene therapy.
authors.affiliation: Department of Urology, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Han
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Guo-jun
authors.initials: GJ
authors.lastname: Zhang
authors.forename: Kun-feng
authors.initials: KF
authors.lastname: Guo
authors.forename: Guang-yi
authors.initials: GY
authors.lastname: Shan
authors.forename: Chui-ze
authors.initials: CZ
authors.lastname: Kong
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics* / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase